scholarly journals Maternal Serum Angiogenic Factor sFlt-1 to PlGF Ratio in Preeclampsia: A Useful Marker for Differential Diagnosis and Prognosis Evaluation in Chinese Women

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-zhen Lou ◽  
Fang Jiang ◽  
Jing Hu ◽  
Xiao-xu Chen ◽  
Ying-na Song ◽  
...  

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.

2020 ◽  
Vol 48 (4) ◽  
pp. 395-401
Author(s):  
Duygu Adiyaman ◽  
Bahar Konuralp Atakul ◽  
Melda Kuyucu ◽  
Gizem Toklu ◽  
Hakan Golbasi ◽  
...  

AbstractObjectiveTo investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR).MethodsThis retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n = 14) and late-onset (n = 83) FGR and those with uncomplicated pregnancies (n = 150) were compared.ResultsThe median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 7.35 (IQR 3.65), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P = 0.047 and P = 0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P = 1.00).ConclusionAs a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset FGR. However, more studies are needed to define the “lower” limit.


2021 ◽  
Vol 8 ◽  
Author(s):  
Benshuo Cai ◽  
Xiaoying Yuan ◽  
Xingmin Li ◽  
Jun Xu ◽  
Juan Du

Background: The association between misfolded proteins presented in the urine of pregnant women and pregnancy outcomes associated with early-onset pre-eclampsia (PE) remains unclear. This study aimed to investigate this association to examine the predictive value of urinary congophilia in the prognostication of pregnancy outcomes in this patient group in the Chinese population.Materials and Methods: This study included 1,397 patients, of which 46, 147, and 8 patients had gestational hypertension, PE, and chronic hypertension, respectively, and 1,196 were healthy controls undergoing the CapCord test for urinary congophilia. Patients with PE were divided into early- and late-onset groups. Patients with early-onset PE were further divided into iatrogenic prematurity and full-term delivery groups, the rates of urinary congophilia were compared between the groups; additionally, this patient group was divided into positive and negative urinary congophilia groups, clinical characteristics and pregnancy outcomes were compared between the groups. Univariate and multivariate logistic regression analyses were performed.Results: A total of 113 (76.9%) of 147 patients in the PE group had urinary congophilia; this rate was higher than that observed in the other three groups (χ2 = 780.892, p < 0.001). Gestational age in the early-onset PE group at both onset and delivery was lower than that in the late-onset PE group (p < 0.001). The rates of iatrogenic prematurity and hemolysis, elevated liver enzymes, and low platelet count syndrome were both higher in the early-onset PE group than in the late-onset PE group (p < 0.001, p < 0.05). In addition, the rate of urinary congophilia in the early-onset PE group was higher than that in the late-onset PE group (χ2 = 13.297, p < 0.001). Urinary congophilia was an independent risk factor for iatrogenic prematurity among patients with early-onset PE in both univariate [odds ratio (OR) 17.143, 95% confidence interval (CI): 4.719–62.271; p < 0.001] and multivariate (OR 18.174; 95% CI: 4.460–74.063; p < 0.001) analyses. Patients with early-onset PE and urinary congophilia were more likely than their counterparts without urinary congophilia to deliver at a lower gestational age, present with iatrogenic prematurity, and have a shorter latency period between onset and delivery.Conclusion: Urinary congophilia confirmed with the CapCord test may help predict pregnancy outcomes in patients with early-onset PE.


2021 ◽  
Vol 5 (2) ◽  
pp. 139
Author(s):  
Widya Retno ◽  
Ivon Diah Wittiarika ◽  
Muhammad Aldika Akbar

 Abstract Background: Preeclampsia is one of the biggest causes of maternal-fetal morbidity and mortality. Based on the prognosis, the classification of Preeclampsia is early onset (<34 weeks) and late onset (> 34 weeks). Purpose: to investigate the relationship between the onset of severe Preeclampsia and perinatal complications. Method: This research is a quantitative study with a retrospective observational analytic study type and collected medical record data. The study population was severe Preeclampsia  patients who gave birth at RUMKITAL Dr. Ramelan Surabaya for the period January 2018 - June 2020 and has no previous history of chronic hypertension. The research sample was 79 subjects with 44 subjects early onset, and 35 subjects late onset. Perinatal complications  examined are preterm delivery, asphyxia, LBW, IUGR, stillbirth. The chi-square test or Fisher’s Exact Test was used to analyze relationships. Result: From the results of the study, the comparison of the percentage from early onset and late onset that experienced complications was 93.2% vs 48.6%, p-value = 0.000, OR = 14.5, CI = 3,764–55,635.  At preterm delivery, it was found that 75% vs 28.6%, p-value = 0.000,  OR = 7.5, CI = 2,754-20,422. . In asphyxia, it was found 41.7% vs 31.4%, p-value = 0.46. At LBW, it was found 72.7% vs 17.1%, p-value = 0,000, OR = 12.9, CI = 4,285-38,771. In IUGR, it was found that 15.9% vs 2.9%, p-value = 0.000. In stillbirth, it was found 18.2% vs 0% and p-value = 0.008. Conclusion: the onset of severe Preeclampsia is related with perinatal complications. Complications associated with the onset severe Preeclampsia are preterm, LBW, stillbirth. Meanwhile, complications that are not related with the onset severe Preeclampsia are asphyxia and IUGR  


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
M. Ohadi ◽  
Y. Heshmati ◽  
A. Mirabzadeh ◽  
H.R. Khorram Khorshid ◽  
K. Kamali

Crucial interaction of caveolin-1 (CAV1) with beta- and gamma-secretases, and aberrant expression of the gene encoding this protein in Alzheimer's disease (AD) support a role for CAV1 in the pathophysiology of this disease.We report a novel polymorphic purine complex stretching ~150 bp of genomic DNA at the 1.5 kb upstream region of the human CAV1 gene, alleles and genotypes of which are associated with sporadic late-onset AD. Extra-short alleles were observed in the case group that were absent in the control subjects. Increased homozygosity for haplotypes was also observed at this region in the Alzheimer's cases, for those alleles and allele lengths shared by the case and control groups [(c2=30.75, df=1, p< .000, OR=4.54, CI 95% (2.56-8.3)]. This region contains GGAA and GAAA motifs, the consensus binding sites for the Ets and IRF family transcription factors, respectively, and is highly conserved in distantly-related non-human primates in respect with location and motif sequence. The effect of this complex sequence on the expression of CAV1, and the related mechanisms in the pathophysiology of AD remain to be clarified.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e025528
Author(s):  
Yi Zhang ◽  
Yong Yang ◽  
Leixi Xue ◽  
Jian Wen ◽  
Lin Bo ◽  
...  

ObjectiveTo investigate the clinical characteristics of patients with early-onset hyperuricaemia (HUC).MethodsA retrospective study using data from the Second Affiliated Hospital of Soochow University was conducted. 623 patients with HUC were divided into early-onset group and late-onset group. Another 201 healthy subjects ≤40 years old were regarded as control group. The data of physical measurements and biochemistry test were collected. Clinical data of early-onset group were compared with late-onset group and control group by analysis of variance (ANOVA) and χ2test. Principal component analysis (PCA) was applied. Logistic regression was used to identify the clinical factors correlated with patients with early-onset HUC.ResultsThe patients of early-onset group had different body mass index (BMI), serum albumin, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), gamma-glutamyltransferase (GGT), creatinine (Cr), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), TG/high density lipoprotein (HDL) ratio, HDL and percentage of males, hypertension (HBP) as well as fatty liver compared with healthy people in the control group. Early-onset group patients had different albumin, ALT, fasting blood glucose, Cr, percentage of males and HBP compared with late-onset group patients. PCA identified four significant patterns including PC1 (labelled ‘TG and HDL’), PC2 (labelled ‘fatty liver and liver enzymes’), PC3 (labelled ‘TC and LDL’) and PC4 (labelled ‘AKP’). The results of univariate and multivariate logistic regression analysis showed that BMI, HBP and albumin were correlative factors for early onset of HUC when the patients with early-onset and late-onset HUC were involved, while gender, BMI, PC1, PC2 and PC4 were correlative factors for early-onset HUC when the early-onset and control groups were involved.ConclusionThis study described a group of patients with early-onset HUC with distinct clinical features. Gender, BMI, ‘TG and HDL’, ‘fatty liver and liver enzymes’ and ‘AKP’ have higher values than HBP, type 2 diabetes mellitus and ‘TC and LDL’ in patients under 40 years old with early-onset HUC.


2019 ◽  
Vol 16 (2) ◽  
pp. 115-122 ◽  
Author(s):  
Jianhao Xiao ◽  
Xiaodong Li ◽  
Qian Yuan ◽  
Simiao Zhang ◽  
Kun Qu ◽  
...  

Objective: Paraoxonase (PON) family genes are closely related to the etiology and prognosis of cerebral infarction. This study explored the association of the promoter methylation of PON family genes (PON1, PON2 and PON3) with the risk of cerebral infarction. Materials and methods: In this study, 152 patients with confirmed cerebral infarction were selected as the case group, and 152 healthy controls were selected as the control group. The quantitative methylation-specific PCR (qMSP) was used to determine the promoter methylation levels of PON1, PON2 and PON3 genes. The methylation level was expressed as a methylation reference percentage (PMR). Results: Our results indicated that PON1 methylation was significantly higher in the case group than in the control group (P = 0.0001). On the contrary, PON3 methylation was significantly lower in the case group than in the control group (P = 0.002). In addition, we found that PON2 gene had a very low level of methylation in both case and control groups (PMR = 0). Subgroup analysis showed that PON1 and PON3 methylation were associated with cerebral infarction only in males (PON1, P = 0.0002; PON3, P = 0.007). Interestingly, the methylation levels of PON1 and PON3 were correlated with each other (case: r = 0.418, P = 0.0001; control: r = 0.3, P = 0.0002). Further multiple regression analysis suggested that elevated methylation levels of PON3 were a protective factor for cerebral infarction [OR (95%CI) = 0.979 (0.96, 0.999), β = -0.021, P = 0.035)], highdensity lipoprotein (HDL) and uric acid (UA) also were protective factors for cerebral infarction [HDL, OR (95% CI) = 0.01 (0.003, 0.033), P < 0.0001); UA, OR (95% CI) = 0.995 (0.991, 0.998), P = 0.003)]. The ROC curve analysis found that the combination of PON3, HDL, and UA had a good predictive power for cerebral infarction (AUC=0.878, 95% CI=0.839-0.918, sensitivity 73.7%, specificity 89.7%, P < 0.0001). Conclusion: PON1 and PON3 promoter methylation levels in peripheral blood were closely related. PON1 and PON3 methylation were associated with the risk of cerebral infarction in men. PON3 promoter methylation combined with HDL and UA could be used as potential biomarkers for the diagnosis of cerebral infarction.


2011 ◽  
Vol 300 (5) ◽  
pp. R1221-R1229 ◽  
Author(s):  
Vaughn A. Browne ◽  
Lilian Toledo-Jaldin ◽  
R. Daniela Davila ◽  
Luis P. Lopez ◽  
Henry Yamashiro ◽  
...  

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (QUA). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600–4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ∼0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. QUAwas lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left QUAwas consistently greater than right in NORM, but the pattern reversed in PE. Although QCIand QEIwere higher in PE and GH than NORM, the fraction of QCIdistributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced QUA( R2= 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited QUAand restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of QUAand pelvic blood flow in early- vs. late-onset PE in high-altitude residents.


2015 ◽  
Vol 42 (7) ◽  
pp. 1141-1149 ◽  
Author(s):  
Alfredo Leaños-Miranda ◽  
Inova Campos-Galicia ◽  
María Guadalupe Berumen-Lechuga ◽  
Carlos José Molina-Pérez ◽  
Yolanda García-Paleta ◽  
...  

Objective.To investigate whether angiogenic factors are associated with risk of developing preeclampsia in pregnant women with systemic lupus erythematosus (SLE).Methods.We performed a nested case–control study within a cohort of SLE women with singleton pregnancies. The study included 42 patients with SLE who eventually developed preeclampsia and 75 normal SLE pregnancies. Serum samples were collected at 4-week intervals (from weeks 12 to 36). Serum samples were analyzed for soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng).Results.Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 and sEng levels, and a higher sFlt-1/PlGF ratio than normal pregnancies. These changes became significant at 12 weeks in patients destined to develop either early onset (< 34 weeks, p ≤ 0.003) or late-onset preeclampsia (≥ 34 weeks, p ≤ 0.02). The risk to develop preeclampsia was higher among patients with PlGF concentration values in the lowest quartile or with sFlt-1 and sEng levels, and sFlt-1/PlGF ratio, in the highest quartile of the normal SLE pregnancies distribution. The OR were higher and appeared earlier in patients destined to develop early onset preeclampsia (OR ≥ 16.2, from Week 12 onward) than in patients who presented preeclampsia later (OR ≥ 8.9, from Week 24 onward).Conclusion.Changes in circulating concentrations of sFlt-1, PlGF, sEng, and the sFlt-1/PlGF ratio precede the onset of preeclampsia in SLE pregnancies. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested earlier or later.


Author(s):  
José S. Cortés ◽  
Paula X. Losada ◽  
Laura X. Fernández ◽  
Emilce Beltrán ◽  
Isabel DeLaura ◽  
...  

Objective The aim of this study is to determine the utility of C reactive protein (CRP) and interleukin (IL)-6 in the diagnosis of neonatal sepsis (NS) in a neonatal intensive care unit (NICU) in the south of Colombia. Study Design A nonmatched case–control study was conducted. Convenience sampling was performed. Data were obtained from clinical records. IL-6 levels were determined using enzyme-linked immunosorbent assay. Receiver operator characteristic (ROC) curve analysis and Youden's index were used to determine the optimal cutoffs for CRP and IL-6 levels in diagnosing NS, early-onset NS (EONS), and late-onset NS (LONS). Results Data from 31 cases and 62 controls were included. History of chorioamnionitis (infinite odds ratio [OR] [3.07-infinity]), and the presence of meconium-stained amniotic fluid during birth (OR: 9.04 [1.35–112]) were identified as risk factors for NS. Differences in CRP (p < 0.0001) and IL-6 (p < 0.0485) levels were also found, more significantly for LONS and EONS patients, respectively. In the diagnosis of LONS using CRP levels, the area under the ROC curve (AUC) was 0.8371 (p < 0.0001). The optimal cutoff was 0.53 mg/dL. For EONS diagnosis using IL-6, the AUC was 0.6869 (p = 0.0315) and the optimal cutoff was 17.75 pg/mL. Conclusion Differences between CRP and IL-6 levels were found between control and NS groups. Furthermore, CRP showed greater potential diagnostic utility in the LONS group, whereas IL-6 showed greater potential utility in the EONS group. Key Points


2019 ◽  
Vol 57 (9) ◽  
pp. 1339-1348 ◽  
Author(s):  
Holger Stepan ◽  
Martin Hund ◽  
Peter Dilba ◽  
Johanna Sillman ◽  
Dietmar Schlembach

Abstract Background For pregnant women with suspected preeclampsia, the soluble fms-like tyrosine-kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio is a biomarker to aid diagnosis. We performed method comparisons between Elecsys® and Kryptor sFlt-1 and PlGF immunoassays and assessed the diagnostic performance for preeclampsia. Methods Serum samples from a case-control study involving 113 pregnant women with preeclampsia/elevated liver enzymes and low platelet count (HELLP) and 270 controls were analyzed. sFlt-1 and PlGF were measured using Roche Elecsys® and BRAHMS Kryptor sFlt-1/PlGF immunoassays. The sFlt-1/PlGF ratios were calculated, and Passing-Bablok regression/Bland-Altman plots were performed. Gestation-specific cut-offs, ≤33 and ≥85/≥110, were assessed. Results Mean (±2 standard deviation [SD]) differences between the Elecsys® and Kryptor values were: sFlt-1, 173.13 pg/mL (6237.66, −5891.40); PlGF, −102.71 pg/mL (186.06, −391.48); and sFlt-1/PlGF, 151.74 (1085.11, −781.63). The Elecsys® and Kryptor immunoassays showed high correlation: Pearson’s correlation coefficients were 0.913 (sFlt-1) and 0.945 (PlGF). Slopes were 1.06 (sFlt-1) and 0.79 (PlGF), resulting in ~20% lower values for Kryptor PlGF. Sensitivities and specificities using the sFlt-1/PlGF ≥85 cut-off for early-onset preeclampsia (20 + 0 to 33 + 6 weeks) were 88.1%/100.0% (Elecsys®) and 90.5%/96.2% (Kryptor), respectively, and using the ≥110 cut-off for late-onset preeclampsia (≥34 + 0 weeks) were 51.3%/96.5% (Elecsys®) and 78.9%/90.1% (Kryptor), respectively. Using Elecsys® and Kryptor sFlt-1/PlGF, 0% and 3.8% of women, respectively, were falsely ruled-in for early-onset, and 3.5% and 9.9%, respectively, for late-onset preeclampsia. Conclusions Despite high correlation between the Elecsys® and Kryptor immunoassays, we observed significant differences between sFlt-1/PlGF and PlGF results. Therefore, sFlt-1/PlGF cut-offs validated for Elecsys® immunoassays are not transferable to Kryptor immunoassays.


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