Placental Growth Factor Levels Research Articles

The clinical value of PlGF and the sFlt1/PlGF ratio in the management of hypertensive pregnancy disorders: A retrospective real-world study in China

IntroductionThe soluble fms-like tyrosine kinase 1 (sFlt1)/placental growth factor (PlGF) ratio is a useful parameter for the diagnosis of preeclampsia. However, a comprehensive comparison of the ratio in preeclampsia and other hypertensive disorders of pregnancy was still missing and the dynamic levels of PlGF in the process of these diseases needed more clinical evidence. MethodsThis retrospective study included participants tested for serum sFlt1 and PlGF levels at a national hospital in China throughout 2020. Diagnostic performance of the sFlt1/PlGF ratio and blood pressure was assessed by the receiver operating characteristic (ROC) analysis. The correlation of the sFlt1/PlGF ratio with pregnancy outcomes was evaluated using Kaplan-Meier curves. Besides, the circulating levels of PlGF were monitored in the time course of different hypertensive disorders' progress. ResultsThe sFlt1/PlGF ratios were significantly elevated in the women with preeclampsia. The results of ROC analysis showed that, compared with blood pressure, the ratio is reliable for preeclampsia diagnosis from healthy control and shows better performance in distinguishing preeclampsia from other hypertensive disorders of pregnancy. A higher ratio than 85 could be used as an indicator of developing severe preeclampsia with adverse outcomes such as preterm delivery. Besides, our results suggested that using PlGF to predict preeclampsia should after 20 weeks of pregnancy. ConclusionThe PlGF and sFlt1/PlGF ratio are worth implementing in clinical management of women with preeclampsia rather than other hypertensive disorders of pregnancy.

Corneal neovascularization inhibition and wound healing impregnability of conbercept on rabbit cornea after penetrating keratoplasty

Purpose The inhibitory effect of conbercept on corneal neovascularization (CNV) after penetrating keratoplasty (PKP) and its effect on postoperative wound healing and corneal strength recovery was investigated. Methods New Zealand white rabbits were randomly divided into 3 groups, two experimental arms A and B and one control arm C. Topical conbercept and subconjunctival injection were carried out respectively after PKP. Slit lamp microscope was used to observe the growth of CNV. The expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and vimentin (Vim) were determined via real-time quantitative polymerase chain reaction (RT-qPCR). The placenta growth factor and vimentin, determination of corneal biomechanical machine strength changed. To measure the maximal strength of the corneal, uniaxial tensile test was carried out on the electroforce 3220-AT biomechanics machine. Results Two weeks after PKP, CNV appeared, inflammatory cell infiltration and new blood vessel formation were observed in the corneal stroma and superficial stroma layer. Compared with the control arm, the expression levels of VEGF and PlGF in the experimental arms were significantly decreased after using conbercept (P < 0.05), and the expression levels reached the maximum at the 4th week and then decreased gradually. The expression level of Vimentin and corneal intensity increased gradually over time. Conclusion Conbercept effectively inhibited the formation of CNV after PKP in rabbits, and did not affect postoperative wound healing, nor did it affect postoperative corneal strength recovery.

Analysis of Causes and Results of Fetal Growth in Utero Caused by Genetic Factors Detected by Ultrasound.

In order to investigate the value of the ultrasonic monitoring of maternal and fetal vascular parameters, serum vitamin D, and placental growth factor (PLGF) in predicting fetal growth restriction (FGR), a method of ultrasonic detection of genetic factors causing fetal growth in utero was proposed. 125 pregnant women with FGR diagnosed in our hospital from June 2018 to June 2021 (the FGR group) and 125 pregnant women with a normal prenatal examination (the control group) were collected retrospectively. The systolic/diastolic blood flow ratio (S/D), pulsatile index (PI), and resistance index (RI) of the fetal umbilical artery (UA), middle cerebral artery (MCA), and maternal uterine artery (UtA) were monitored by ultrasound at 20 to 24 weeks of gestation, and the levels of serum vitamin D and PLGF were detected. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of FGR. The results showed that the S/D, PI, and RI of UA in the FGR group were higher than those in the control group, the areas under the curve (AUC) were 0.866, 0.817, and 0.849, and the sensitivity and specificity were (72.8%, 91.2%), (50.4%, 100%), and (72.8%, 91.2%), respectively. The S/D, PI, and RI of MCA were lower than those of the control group. The AUC was 0.882, 0.869, and 0.834, respectively; the sensitivity and specificity were (92.0%, 74.4%), (88.8%, 81.6%), and (90.4%, 72%), respectively. The S/D, PI, and RI of UtA were higher than those of the control group; the AUC was 0.768, 0.729, and 0.732; the sensitivity and specificity were (91.2%, 52%), (48%, 90.4%), and (48.8%, 90.4%), respectively. The serum levels of vitamin D and PLGF were lower than those of the control group (AUC 0.784 and 0.807), and the sensitivity and specificity were (54.4%, 91.2%) and (99.2%, 52%), respectively. It was concluded that the ultrasound monitoring of UA, MCA, and UtA in pregnant women in the middle of pregnancy and detection of serum vitamin D and PLGF levels had a certain predictive value for FGR. Moreover, the comprehensive evaluation could reduce the occurrence of FGR in high-risk pregnant women.

Prediction performance of serum placental growth factor (PLGF) human chorionic gonadotropin β (β-hCG) and PAPP-A levels in early pregnancy for pregnancy outcomes.

Objectives:To investigate the prediction performance of serum placental growth factor (PLGF), free human chorionic gonadotropin β (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels in early pregnancy for pregnancy outcomes.Methods:A total of 4256 pregnant women who underwent obstetric examinations in our hospital from June 2018 to June 2020 and completed their full pregnancy were included in the study. The clinical pregnancy outcomes of pregnant women with different PLGF, PAPP-A and β-hCG levels in early pregnancy were recorded, and the prediction performance of the above indicators for adverse pregnancy outcomes was discussed.Results:Pregnant women with increased or decreased PLGF or increased PAPP-A or β-hCG had significantly higher incidence of adverse pregnancy outcomes than normal pregnant women. Pregnant women with abnormal pregnancy had significantly higher β-hCG and PLGF, and lower PAPP-A than those with normal pregnancy. The sensitivity of serum PLGF, β-hCG and PAPP-A in early pregnancy for predicting adverse pregnancy outcomes was 95.13%, 94.19% and 97.75%, and the specificity was 84.31%, 85.80% and 83.22%, respectively.Conclusions:Serum PLGF, PAPP-A and β-hCG in early pregnancy are more effective in predicting adverse pregnancy outcomes. Clinical monitoring of patients with increased PLGF, decreased PAPP-A, and increased β-hCG should be strengthened, especially the monitoring of antepartum examination and B-ultrasound detection of pregnant women with abnormal indicators in middle and late pregnancy, so as to identify adverse pregnancy outcomes as early as possible and give targeted intervention.

PREGNANCY OUTCOMES IN WOMEN WITH EXTREMELY HIGH SFLT-1/PIGF RATIO: CASE SERIES

Preeclampsia (PE) is a multisystem disorder, usually defined as the development of hypertension and proteinuria after 20 weeks of pregnancy. The sFlt-1/PlGF ratio has been widely studied as a diagnostic and prognostic marker of preeclampsia and other manifestations of placental dysfunction. A sFlt-1/PlGF ratio greater than 85 for early PE, &lt;34 weeks of gestation suggests a high risk of PE requiring close clinical monitoring. Our main aim was to evaluate the maternal and perinatal outcomes of pregnancies with an extremely high sFlt-1/PlGF ratio. The analysis included data on placental growth factor and soluble fms-like tyrosine kinase serum levels, measured during 2017–2020 in 128 pregnant women. Here we present 8 cases of women with a numerical ratio greater than 850. In all 100% of cases, the signs of obstetric angiogenic catastrophe requiring imminent delivery developed soon. We observed a trend for worsening perinatal outcomes in women with an extremely high sFlt-1/PlGF of ≥850.

Peculiarities of blood flow in the uterine arteries, factors of angiogenesis, hormonal profile and their relationships in pregnant women with hypertension

The objective: to assess and establish the relationships between Doppler blood flow indicators in the uterine arteries, angiogenesis factors and hormones of the mother-placenta-fetus system in pregnant women with arterial hypertension I-II degree.Materials and methods. A prospective study of 88 pregnant women at 11–12 weeks of gestation was carried out: 61 pregnant women with chronic arterial hypertension (CH) of the I–II degree (main group) and 27 healthy pregnant women with physiological pregnancy (control group). All patients have been examined: blood flow Doppler in the left and right uterine arteries – pulsation index (PI), resistance index (IR) and systolic-diastolic ratio (SDR). Chorionic gonadotropin (HCG), progesterone (PG), estradiol (E) and angiogenesis indices (placental growth factor (PlGF) as a pro-angiogenic factor) and placental-soluble fms-like tyrosine kinase (sFlt-1) as an anti-angiogenic factor and the ratio of sFlt-1/PlGF) were determined in blood. Statistical analysis was performed using the program “STATISTICA 13”.Results. There was no statistically significant difference in SDR and IP indicators between the groups. PI values in the right uterine artery in pregnant women of the main group were significantly higher than the indicator of healthy pregnant women (1.73 (1.65; 1.8) units versus 1.33 (1.1; 1.49) units, respectively). The PI values in the left uterine artery in pregnant women with CAH also significantly differed from those in women with the physiological course of pregnancy (1.7 (1.66; 1.79) units and 1.35 (1.22; 1.51) units, respectively). A significant correlation between SDR indicators and markers of angiogenesis and hormonal profile in women of the main group has not been established. In pregnant women with CAH, an inverse relationship was observed between PI and PlGF (mean strength R=-0.34 for PI in the right uterine artery and R= -0.41 for PI in the left uterine artery), respectively, between PI and sFlt-1/PlGF – direct relationship (average strength R=+ 0.37 for PI in the right uterine artery and R=+0.43 for PI in the left uterine artery). In women with the physiological course of pregnancy and childbirth, the PI value in the right uterine artery correlated with the sFlt-1/PlGF ratio (direct relationship) and PlGF level (feedback). PI in the left uterine artery had a direct relationship with the value of the sFlt-1/PlGF ratio. In pregnant women with CAH, the PlGF level decreases, while the PI value, on the contrary, increases.Conclusions. The significant differences between the indicators of SDS and IR in pregnant women with CAH and pregnant women without CAH have not been established. In women with CAH, significantly higher PI values were found in the right and left uterine arteries compared to those in women without CAH. The course of pregnancy in women with CAH is accompanied by a shift in the balance between pro- and anti-angiogenic factors, as evidenced by a statistically significant increase in sFlt-1 level against the background of a decrease in PlGF level, as well as a corresponding increase in the sFlt-1/PlGF ratio as compared with pregnant women without CAH. There are no correlations between indicators of SDR and IR in the uterine arteries, markers of angiogenesis and hormonal profile in pregnant women with and without CAH. Nevertheless, PI values in the right and left uterine arteries correlate with the PlGF level (feedback) and the sFlt-1/PlGF ratio (direct relationship) in pregnant women with CAH. This indicates the presence of disorders in this contingent of women in the I trimester of pregnancy.

Assessment of the value of measuring soluble fms-like tyrosine kinase-1 and placental growth factor levels following administration of tadalafil to treat fetal growth restriction

Purpose The aim of this study was to measure the blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) before and after tadalafil treatment in patients with fetal growth restriction. Materials and methods Maternal blood was collected from 13 women before and 2 weeks after tadalafil administration in the TADAFER II trial. The tadalafil treatment was conducted in addition to the conventional FGR treatment. As a control, maternal blood was also collected from 11 women before and 2 weeks after conventional treatment for fetal growth restriction. Blood sFlt-1 and PlGF were measured and the sFlt-1/PlGF ratio was calculated. Student’s t-test was used to statistically analyze differences in the sFlt-1 and PlGF levels, and in the sFlt-1/PlGF ratios. Results In both treatment groups, the levels of sFlt-1 and PlGF before and after treatment were not significantly different from each other. The sFlt-1/PlGF ratio was 2.0 ± 1.0 before and 17.6 ± 11.3 after treatment in the control group (p=.04). The sFlt-1/PlGF ratio was 2.2 ± 1.1 before and 22.2 ± 10.6 after tadalafil treatment in the tadalafil group (p=.06). The sFlt-1/PlGF ratios before and after tadalafil treatment were significantly increased in the control group. In both treatment groups, the sFlt-1/PlGF ratios before and after treatment were less than 38. Conclusions We conclude that the levels of sFlt-1 and PlGF were not significantly different as a result of tadalafil treatment. Further studies are needed to understand the mechanism of action of tadalafil in the treatment of fetal growth restriction.

Association between serum placental growth factor and vascular endothelial function in hyprtensive disorders complicating pregnancy.

Hypertensive disorders complicating pregnancy (HDCP) is a systemic disease among pregnant women. Therefore, the prevention and prediction of hypertension during pregnancy are critical. This study aimed to clarify whether the vascular endothelial function of women with gestational hypertension was linked to placental growth factor. A total of 200 pregnant women were enrolled in our study and subsequently divided into two groups: the HDCP group and the normal pregnancy controls. The levels of serum placental growth factor, as well as plasma endothelin-1 and nitric oxide, between the two groups were measured. In addition, the endothelial function indexes, including pressure-strain elasticity coefficient (EP), the common carotid stiffness index (β), arterial compliance, single-point pulsed-wave velocity, and augment index (AI) of bilateral common carotid arteries, were compared between the HDCP and control groups using the echo tracking technique. In our study, the level of placental growth factor in the HDCP group was significantly lower than the control group. Furthermore, our results clarified that endothelin-1 increased while nitric oxide decreased in the HDCP group compared with the control group. On the other hand, we found that EP, β, pulsed-wave velocity and augment index values were significantly higher in the HDCP group than in the control group (P < 0.001). However, the value of arterial compliance was significantly decreased in patients of the HDCP group compared with the control group (P < 0.001). In conclusion, the association between serum placental growth factor and vascular endothelial function in HDCP could serve as a more accurate predictive factor of pregnant hypertension.

Vascular and inflammatory plasma biomarkers correlate with human post‐mortem cerebral vascular pathology

AbstractBackgroundVascular Cognitive Impairment and Dementia (VCID) is a common cause of dementia in Western populations. Small‐vessel disease (SVD), a VCID subtype, can present as arteriolosclerosis and microinfarcts. Currently, identifying this pathology clinically is limited to MRI, which is expensive, limited in terms of small vessel resolution and not widely available. Therefore, a more accessible screening tool is needed to clinically evaluate SVD. Here, we evaluate the relationships between vascular and inflammatory plasma biomarkers with global levels of SVD pathology in human brain.MethodPlasma and brain tissue samples were obtained from the University of Kentucky Alzheimer’s Disease Research Center (UK‐ADRC) Brain Bank. Cases were selected from participants who had an available plasma sample from within two years of death. These plasma samples were analyzed using a digital immunoassay (Quanterix Simoa) to determine biomarker levels of placental growth factor (PlGF), matrix metalloproteinase 9 (MMP9), and tumor necrosis factor α (TNFα). Biomarker levels were categorized by quartiles. Pathological evaluation was performed by UK‐ADRC neuropathologists, blind to clinical data. The association of plasma markers with neuropathology was estimated via multinomial and binary logistic regressions adjusted for age and sex. Global arteriosclerosis was examined using a scale of none/mild/moderate/severe, with none being the reference. Presence or absence of microinfarcts was also examined.ResultIncluded cases (n=93) were age 82.0±9.2 years at death; 46.7% were female. Higher plasma placental growth factor (PlGF) levels were associated with less severe arteriolosclerosis: odds ratio (OR)=0.8 (95% CI 0.5‐1.3), 0.8 (0.5‐1.5), and 0.6 (0.2‐1.7); higher plasma MMP9 levels were associated with more severe arteriolosclerosis (OR=1.0 (0.5‐2.1), 0.7 (0.3‐1.5), 0.7 (0.2‐2.4), comparing odds of mild, moderate, and severe to none, respectively), though these results were not statistically significant. Lower plasma PlGF and MMP9, and higher TNFa, were associated with higher odds of microinfarction: OR=0.59 (0.33‐1.02), 0.74 (0.38‐1.42), and 2.28 (0.84‐6.20), respectively.ConclusionOur results, while based on a small sample, suggest plasma PlGF and MMP9 levels have an inverse relationship with global SVD pathology, while plasma TNFa is positively correlated with increased global SVD pathology. These results provide support for potential use of plasma biomarkers as a clinical screening tool for SVD pathology.

Associations between cerebrospinal fluid markers of neuroinflammation and longitudinal measurements of white matter lesions

AbstractBackgroundThe interplay between neuroinflammation and small vessel disease in the early stages of neurodegenerative disease is unclear. Here, we tested the association between cerebrospinal fluid (CSF) levels of biomarkers reflecting inflammatory processes and white matter lesion (WML) volume over time.MethodWe included 582 cognitively unimpaired (CU) elderly and 279 patients with mild cognitive impairment (MCI). CSF samples were analyzed for interleukin (IL)–6, IL‐7, IL‐8, IL‐15, IL‐16, interferon‐gamma induced protein‐10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), intercellular adhesion molecule 1(ICAM‐1), vascular adhesion molecule 1 (VCAM‐1), placental growth factor (PlGF), and fms‐related tyrosine kinase 1 (sFlt‐1) as well as vascular endothelial growth factor (VEGF). WML volumes were measured at baseline, and at 2, 4 and 6 years. Analyses were adjusted for Aβ status, age and gender.ResultIn CU, lower levels of PlGF (β=‐0.02, p=0.027) were associated with increasing WML burden over time. However, in MCI lower levels of PlGF (β=‐0.05, p&lt;0.001), IL‐16 (β=‐0.04, p=0.010), VEGF (β=‐0.03, p=0.012), IL‐6 (β=‐0.04, p=0.005), IL‐8 (β=‐0.03, p=0.016) and MCP‐1 (β=‐0.03, p=0.012), as well as higher levels of sFlt‐1 (β=‐0.03, p=0.034) were associated with longitudinal increase in WML.ConclusionCSF markers mediating angiogenesis, such as PlGF and VEGF, are associated with longitudinal WML volume changes, especially in individuals with MCI.

Dysregulated Serum Lipid Metabolism Promotes the Occurrence and Development of Diabetic Retinopathy Associated With Upregulated Circulating Levels of VEGF-A, VEGF-D, and PlGF.

Purpose: This study aims to explore the correlations of arteriosclerosis-associated plasma indices with various severity levels of diabetic retinopathy (DR) and to test the hypothesis that elevated circulating level of known angiogenic cytokines induced by hyperglycemia is associated with dyslipidemia on DR.Methods: This cross-sectional study consists of 131 patients with type 2 diabetes. The patients were categorized based on their DR status into those with no DR (diabetes mellitus, DM), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) groups. The biochemical profile including fasting glucose, glycated hemoglobin (HbA1c), lipid profile were estimated, plasma angiogenic cytokines (vascular endothelial growth factor, VEGF-A, -C, -D) and placental growth factor (PlGF) were analyzed by protein microarrays. The atherogenic plasma index (API) was defined as low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C); atherogenic index (AI) was calculated as (TC-(HDL-C))/HDL-C and atherogenic index of plasma (AIP) was defined as log (TG/HDL-C).Results: No significant differences were detected in the duration of hypertension, age, and gender between the three groups. Serum TC and LDL-C, AI, and API in the NPDR group and PDR group were significantly higher than those in the DM group. The circulating level of PlGF, VEGF-A, and VEGF-C were significantly correlated with the severity of DR. VEGF-D is a risk factor independent of API (Z = −2.61, P = 0.009) and AI (Z = −2.40, P = 0.016). Multivariate logistic regression showed that AI and API are strong risk factors for the occurrence and severity of DR. Associated with AI and API, VEGF-D and PlGF contribute to DR: VEGF-D [AI: P = 0.038, odd ratio (OR) = 1.38; VEGF-D: P = 0.002, OR = 1.00. API: P = 0.027, OR = 1.56, VEGF-D:P = 0.002, OR = 1.00] and PlGF [AI: P = 0.021, OR = 1.43; VEGF-D: P = 0.004, OR = 1.50. API: P = 0.011, OR = 1.66; VEGF-D: P = 0.005, OR = 1.49].Conclusions: Total cholesterol (TC) and LDL-C are risk factors for presence of any DR. Atherogenic index and API are novel and better predictive indicators for the occurrence and severity of DR in comparion with the traditional lipid profiles. Abnormal lipid metabolism are associated with the upregulation of circulating cytokines that are linked to the severity of DR.

Maternal vitamin D deficiency reduces docosahexaenoic acid, placental growth factor and peroxisome proliferator activated receptor gamma levels in the pup brain in a rat model of preeclampsia

Background: Preeclampsia is a pregnancy disorder characterized with abnormal placental angiogenesis. Vitamin D and long chain polyunsaturated fatty acids (LCPUFA) play a crucial role in pregnancy and are required for normal placental and fetal growth and development. This study reports the effect of maternal vitamin D on LCPUFA levels in the mother and offspring brain fatty acid levels and angiogenic markers in a rat model of preeclampsia.Methods: Female rats were divided into four groups from pre-pregnancy to pregnancy, viz Control; Preeclampsia (PE); Vitamin D deficient with PE (VDD-PE) and Vitamin D supplemented with PE (VDS-PE). Preeclampsia was induced by administering l-nitroarginine methyl ester (L-NAME) at the dose of 50 mg/kg body weight/day from day 14 to day 19 of gestation. Dams were sacrificed at d20 of gestation to collect dam blood, placenta and pup brain. LCPUFA levels from dam plasma, erythrocytes and placenta and its transcription factor peroxisome proliferator activated receptor gamma (PPAR-g) from placenta were estimated. Pup brain LCPUFA levels, angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and transcription factor hypoxia inducible factor (Hif-1α) and PPAR-g were also estimated.Results: Maternal vitamin D status influences fatty acid levels. Placental PPAR-g levels were lower in the VDD-PE group as compared to the VDS-PE groups (p < 0.01). In the offspring brain, both PE and VDD-PE group showed lower levels of DHA (p < 0.05 for both) while saturated fatty acids (SFA) levels in the VDD-PE group were higher as compared to the control group (p < 0.05). VDD-PE group also showed lower levels of PlGF and PPAR-g (p < 0.01 and p < 0.05, respectively) in the pup brain while vitamin D supplementation demonstrated levels similar to control.Conclusion: This study for the first time demonstrates that maternal vitamin D status influences LCPUFA metabolism and angiogenesis in the offspring brain.

Correlation between 25-Hydroxyvitamin D, sFlt-1, PLGF, and Hypertension in Pregnancy.

Gestational hypertension is a common disease in clinical practice, which does great harm to the mother and infant. The purpose of this study was to investigate the relationship between 25-hydroxyvitamin D, sFlt-1, and PLGF and hypertensive disorder complicating pregnancy. Specimen preparation: after delivery or placental caesarean section, in order to avoid calcification and necrosis in the middle of the placenta, an area of about 1.5 cm × 1.5 cm × 1.5 cm should be separated immediately. After dehydration, use a Citadel 2000 dryer to dry it and place it in a block of saline for xylene immunohistochemical staining. Statistical processing was performed according to the proportion of positive cells in each part and the depth of staining. Placental tissue collection and treatment: within 20 minutes after the delivery of the placenta, two pieces of the placental tissue (about 1.0 cm × 1.0 cm × 1.0 cm) were taken from the central zone of the placental maternal surface without obvious bleeding and calcification. They were rinsed repeatedly in normal saline, fixed in 10% neutral formaldehyde solution for 24 hours, dehydrated using an automatic dehydrator, and embedded in paraffin for detection. Before the study, 20 ml of distilled water was added to the sample to stand for 20 minutes; the Cobas E610 immunoanalyzer was turned on, and sFlt-1 and PLGF (placental growth factor) were selected. The serum 25-hydroxyvitamin D level of pregnant women was detected in the fasting state at 24–28 weeks of gestation, and the best collection time was 8 : 00–11 : 00 in the morning. 5 ml of the whole blood sample without anticoagulant was collected and stored at 0–4°C in a cold storage and dark environment. The serum was obtained by high-speed centrifugation within 24 hours after collection. The method is suitable for the quantitative determination of 25-OH-vitamin D in human serum. In the hypertensive pregnancy group, the level of 25-hydroxyvitamin D was 18.44 ± 3.48 ng/ml, and the sFlt-1/PLGF level was highest at 0–5 weeks followed by 5–10 weeks, 10–15 weeks, and 15–20 weeks. This study provides new ideas and experimental clues for the prevention and treatment of pre-eclampsia.

Do Patients with A History of Pre-Eclampsia Have Elevated Levels of Coagulation and Angiogenic Markers Postpartum?

Background: Pre-eclampsia (P-EC) is a pregnancy-specific disorder, characterised by placental insufficiency and endothelial dysfunction. It is a significant cause of maternal and fetal morbidity. Women with a history of P-EC have heightened risks of future cardiovascular and thromboembolic disease. In addition, pre- clamptic patients have elevated levels of clotting and angiogenic factors; however it is unclear whether these changes persist postpartum. Aims: The aim of this study was to investigate the relationship between haemostatic as well as angiogenic and anti-angiogenic factors in women with a past-history of P-EC, including vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), in combination with tissue factor (TF) and TF pathway inhibitor (TFPI), also whether these factors were altered postpartum in women with a history of P-EC. Methods: The study followed a case-control design. Blood samples were obtained at 6-12 months postpartum from 21 primiparous women after a pregnancy affected by P-EC, and 21 women with a previously unaffected pregnancy. Plasma concentrations of each of the factors were determined using enzyme-linked immunosorbent assay. Results: Significant differences were not observed in levels of VEGF (p=0.068), PlGF (p=0.333), sFlt-1 (p=0.910), sEng (p=0.612), TF (p=0.260) or TFPI (p=0.786) between women with and without a history of pre-eclampsia. Additionally, no significant difference was found in the TF: TFPI ratio between case and control groups (p=0.734). Conclusion: This study does not support the hypothesis that levels of VEGF, PlGF, sFlt-1, sEng, TF or TFPI are altered in women with a history of P-EC compared to controls. However, we observed a weak positive association between all parameters measured. While we acknowledge that this is a pilot study and that the sample sizes is relatively small, our results suggest that circulating haemostatic, angiogenic and anti-angiogenic factors are not significantly altered in women with a past-history of P-EC.

Aqueous humor analyses of diabetic macular edema patients with subretinal fluid

We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF.

Evaluation of sFlt-1 and PlGF for predicting preeclampsia in pregnant women with diabetes mellitus

AIM: The aim of this study was to evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels in the blood of women with various types of diabetes mellitus, depending on the correction method applied, and to determine the prognostic significance of the sFlt-1 / PlGF ratio for predicting the development of preeclampsia in this patient population.&#x0D; MATERIALS AND METHODS: We examined 140 pregnant women who were included in six main study groups: type 1 diabetes mellitus (with or without pregravid preparation), type 2 diabetes mellitus (diet therapy or insulin therapy), and gestational diabetes mellitus (diet therapy or insulin therapy). The comparison groups consisted of pregnant women with preeclampsia and patients without complications of pregnancy. Using electrochemiluminescence analysis, PlGF and sFlt-1 levels in the blood serum were determined twice, at 11+013+6 and 30+033+6 weeks of gestation. Statistical data processing was performed using the IBM SPSS Statistics version 23 and GraphPad Prism version 8.0 software packages.&#x0D; RESULTS: In the blood serum of pregnant women with diabetes mellitus in the first and third trimesters of pregnancy, we found an increase in sFlt-1 level and a decrease in PlGF level, as well as an increase in the sFlt-1 / PlGF ratio. These changes were most pronounced in individuals with type 1 diabetes mellitus without pregravid preparation and with type 2 diabetes mellitus on insulin therapy. In patients with pregestational types of diabetes mellitus, the sFlt-1 / PlGF ratio was a predictor of preeclampsia already in the early stages of pregnancy. Analysis of the ROC curve showed that the threshold sFlt-1 / PlGF ratio for predicting preeclampsia in pregnant women with diabetes mellitus in the first trimester was 32.5 (sensitivity 92.9%, specificity 50.0%) and in the third trimester 71.8 (sensitivity 85.7%, specificity 82.3%) with AUC 0.78 (95% CI 0.680.88) and 0.89 (95% CI 0.830.95), respectively. In the first trimester, the positive and negative predictive values of the sFlt-1 / PlGF ratio as a predictor of preeclampsia in pregnant women with diabetes mellitus were 63.3% and 97.6%, respectively; in the third trimester, 38.9% and 93.6%, respectively.&#x0D; CONCLUSIONS: Blood level alterations of PlGF and sFlt-1 are characteristic of patients with diabetes mellitus in the first and third trimesters of pregnancy. An increase in the sFlt-1 / PlGF ratio is associated with a higher incidence of unfavorable perinatal outcomes in women with impaired carbohydrate metabolism. Determination of the sFlt-1 / PlGF ratio is a valid method for predicting the development or absence of preeclampsia in women with diabetes mellitus.

Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China.

To evaluate, in a Chinese population, the performance of a screening strategy for preterm pre-eclampsia (PE) using The Fetal Medicine Foundation (FMF)'s competing-risks model and to explore its clinical applicability in mainland China. This was a prospective, multicenter, observational cohort study including 10 899 women with singleton pregnancy who sought prenatal care at one of 13 hospitals, located in seven cities in mainland China, between 1 December 2017 and 30 December 2019. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and maternal serum levels of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation were measured and converted into multiples of the median using Chinese reference ranges. Individualized risk for preterm PE was calculated using the FMF algorithm. Prior risk was calculated based on maternal demographic characteristics and obstetric history. We evaluated the efficiency of the screening strategy using various combinations of biomarkers and analyzed its predictive performance for a composite of placenta-associated adverse pregnancy outcomes, including PE, placental abruption, small-for-gestational age (SGA) and preterm birth, at fixed false-positive rates for preterm PE. We identified 312 pregnancies that developed PE, of which 117 cases were diagnosed as preterm PE (< 37 weeks' gestation). There were 386 pregnancies complicated by severe composite placenta-associated adverse outcome, including preterm PE, 146 cases of severe SGA (birth weight < 3rd percentile) neonate, 61 cases with placental abruption and 109 cases of early preterm birth < 34 gestational weeks. The triple-marker model containing biomarkers MAP, UtA-PI and PAPP-A achieved, at fixed false-positive rates of 10%, 15% and 20%, detection rates for preterm PE of 65.0%, 72.7% and 76.1%, respectively, and detection rates for severe composite placenta-associated adverse outcome of 34.7%, 41.7% and 46.4%, respectively. Replacing PAPP-A with PlGF or adding PlGF to the model did not improve the performance. Of women screening positive for preterm PE at a fixed 5% false-positive rate, an estimated 30% developed at least one placenta-associated adverse pregnancy outcome, including PE, placental abruption, SGA (birth weight < 10th percentile) and preterm birth < 37 weeks. The FMF competing-risks model for preterm PE was found to be effective in screening a mainland Chinese population. Women who screened positive for preterm PE had increased risk for other placenta-associated pregnancy complications. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Sodium butyrate alleviates pre-eclampsia in pregnant rats by improving the gut microbiota and short-chain fatty acid metabolites production.

Pre-eclampsia (PE) affects pregnant patients worldwide, but there is no effective treatment for this condition. We aimed to explore the effect of sodium butyrate (NaB) on PE. In this study, Nω-nitro-L-arginine methyl ester hydrochloride was used to induce PE in pregnant rats. We found that NaB significantly decreased the levels of blood pressure, 24-h protein urine and inflammatory factors (IL-1β, IL-6 and TGF-β), increased the foetal and placental weights and intestinal barrier markers (ZO-1, claudin-5 and occludin) expression. In addition, NaB intervention reduced the levels of soluble fms-like tyrosine kinase 1 and soluble endoglin and increased placental growth factor level. Meanwhile, after NaB treatment, the Treg/Th17 ratio of immune cells in the spleen and small intestine of pregnant rats decreased, while the level of pregnancy-related diamine oxidase increased. Notably, the PE rat treatment with NaB improved gut microbiota compositions, especially for the abundances of Firmicutes and Bacteroides, and significantly increased butyric acid and pentanoic acid levels, which might help to alleviate PE in pregnant rats. In the PE rat model, exogenous NaB improved intestinal barrier function and reduced adverse outcomes, which might be associated with the gut microbiota and its production of SCFA metabolites. NaB might alleviate the adverse outcomes of PE by regulating gut microbiota and its metabolite SCFA, which revealed that NaB might be a potential regulator of gut microbiota and a therapeutic substance for PE.

Abstract 28: Omeprazole Administration To Women With Preterm Preeclampsia: Effects On Circulating Soluble Fms-like Tyrosine Kinase-1, Placental Growth Factor And Endothelin-1 Secretion.

Low soluble Fms-like tyrosine kinase (sFlt-1) has been reported in women with suspected or confirmed preeclampsia (PE) coincidentally using proton pump inhibitors (PPIs), suggesting a role for these agents as potential treatment for PE. Here, we examined whether administration of omeprazole to women with PE could acutely reduce their circulating levels of sFlt-1 or enhance their placental growth factor (PlGF) concentrations. We performed a randomized controlled trial in which women (≥ 18 years) with confirmed preeclampsia and a gestational age between 20 +0 and 34 +6 weeks were allocated to receive 40mg omeprazole once daily or no omeprazole. Blood was collected at baseline and days 1,2,4,8 followed by twice-weekly until delivery. Primary outcome was specified as the difference in sFlt-1 or PlGF 4 days after omeprazole initiation compared to the non-omeprazole group. Secondary outcomes were defined as between-group differences in longitudinal course of sFlt-1 and PlGF and pregnancy outcomes. Between Dec 2018 and June 2021, 50 women with PE were randomized, of which 40 women remained pregnant after 4 days. Mean maternal age was 30 years, and median gestational age was 31 weeks. Baseline sFlt-1 levels did not differ between non-omeprazole (n=20) and omeprazole group (n=20) (10743 vs. 7110pg/mL, p=0.11), neither did the levels of PlGF (p=0.14). After 4 days, sFlt-1 levels remained similar in women receiving omeprazole compared to women not receiving omeprazole (8364 vs. 13017pg/mL, p=0.14), and the same was true for PlGF (90 vs. 55pg/mL, p=0.14). Using linear mixed models, no difference in longitudinal course of sFlt-1 or PlGF could be attributed to the treatment group, when adjusted for baseline values and GA at enrollment (p=0.47). Women receiving omeprazole had a similar length of pregnancy compared with those not receiving this drug (median 15 vs. 14 days, p=0.70). Except for a higher neonatal intubation rate in the non-omeprazole group (31% vs 4%, p=0.02) there were no differences in maternal/perinatal complications between the two groups. Our findings suggest that daily administration of 40mg in women with PE do not alter their circulating levels of sFlt-1 and PlGF, arguing against a role for this drug as a potential treatment for this syndrome.

SY10-3. Complement Activation and Regulation in Preeclampsia and HELLP Syndrome

To evaluate the potential of maternal serum placental growth factor (PlGF) as a marker for Trisomy 21 in Chinese pregnant women.Serum samples were collected and stored from 600 women who have a viable singleton pregnancy and underwent first trimester screening for Trisomy 21 between 2011 and 2014. Serum concentration of PlGF was measured using the automated time-solved immunofluorometric assay and expressed as Multiples of the expected median (MoM) from the 600 women available stored serum samples (558 Euploidy and 42 Trisomy 21). The levels of PlGF MoM were compared between Trisomy 21 cases and Euploid pregnancies. Expected median PlGF levels in Chinese were also compared to that published for Caucasians. Multivariate Gaussian modeling was performed to predict detection and false-positive rates.In euploid pregnancies the concentrations of PlGF increased with Crown Rump Length(CRL) and decreased with maternal weight. The overall median MoM of PlGF in Chinese was higher than that of Caucasian. The median PlGF level was 0.63 MoM in the cases and 1.00 MoM in the controls (p < 0.0001). The prediction of Trisomy 21 has been slightly improved by the addition of PlGF to the standard screening test in China. The detection rate of screening after adding PlGF data was increased from 93.4% to 94.6% at a false-positive rate of 3% and the false positive rate decreased from 0.23% to 0.17% for a detection rate of 80%.The median PlGF concentrations in Chinese is higher than those of Caucasians. Results suggest adding PlGF may substantially improve the performance of current first trimester screening strategy for Trisomy 21 in Chinese pregnant women.