Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

Abstract Background: Preeclampsia is a common obstetric multisystem disorder causing maternal and fetal morbidity and mortality; it’s been shown that the prediction improves preeclampsia outcomes in pregnancy. However, the current serum biomarkers had low clinical application values and still lack validation studies. Here we aimed to evaluate the preeclampsia prediction values of a series of serum biomarkers in Chinese pregnant women of > 20 weeks of gestation. Methods: Singleton pregnant women with preeclampsia-related clinical and/or laboratory presentations were recruited and had blood drawn at their first visits. The prospective cohort was further divided into preeclampsia-positive and preeclampsia-negative groups based on the follow-up results. The following markers were tested using the collected serum samples: soluble fms-like tyrosine kinase-1 (sFlt-1); placental growth factor (PlGF); thrombomodulin (TM); tissue plasminogen activator inhibitor complex (tPAI-C); compliment factors C1q, B, and H; glycosylated fibronectin (GlyFn); pregnancy-associated plasma protein-A2 (PAPP-A2); blood urea nitrogen (BUN); creatinine (Cre); uric acid (UA); and cystatin C (Cysc). Results: A total of 196 women with suspected preeclampsia were recruited with follow-up medical records. Twenty-five percent (n=49) of the recruited subjects developed preeclampsia before delivery, and 75% remained preeclampsia-negative (n=147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). With the cut-off values obtained from the ROC analyses, the positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. Conclusions: Although several serum markers were found to be significantly changed with current prospective cohort, their limited predictive values in preeclampsia development posed potential barrier in clinical implementation. Further studies with larger cohort are warranted to further reveal the clinical utilities of the serum markers in preeclampsia prediction.

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Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

10.21203/rs.3.rs-33584/v2 ◽

2020 ◽

Author(s):

Jing Wang ◽

Honghai Hu ◽

Xiaowei Liu ◽

Shenglong Zhao ◽

Yuanyuan Zheng ◽

...

Keyword(s):

Plasminogen Activator Inhibitor ◽

Serum Levels ◽

Serum Markers ◽

Serum Biomarkers ◽

Operating Characteristics ◽

Serum Samples ◽

Predictive Values ◽

A Prospective Study ◽

Activator Inhibitor

Abstract Background: Preeclampsia prediction improves maternal and fetal outcomes in pregnancy. We aimed to evaluate the preeclampsia prediction values of a series of serum biomarkers. Methods: Singleton pregnant women with preeclampsia-related clinical and/or laboratory presentations were recruited and had blood drawn at their first visits. The prospective cohort was further divided into preeclampsia-positive and preeclampsia-negative groups based on the follow-up results. The following markers were tested using the collected serum samples: soluble fms-like tyrosine kinase-1 ( sFlt-1); placental growth factor (PlGF); thrombomodulin (TM); tissue plasminogen activator inhibitor complex (tPAI-C); compliment factors C1q, B, and H; glycosylated fibronectin (GlyFn); pregnancy-associated plasma protein-A2 ( PAPP-A2); blood urea nitrogen (BUN); creatinine (Cre); uric acid (UA); and cystatin C (Cysc). Results: A total of 196 women with suspected preeclampsia were recruited with follow-up medical records. Twenty-five percent (n=49) of the recruited subjects developed preeclampsia before delivery, and 75% remained preeclampsia-negative (n=147). The serum levels of sFlt-1, BUN, Cre, UA, Cysc and PAPP-A2 were significantly elevated, and the PlGF level was significantly decreased in the preeclampsia-positive patients. In the receiver operating characteristics (ROC) analyses, the area under the curves were listed in the order of decreasing values: 0.73 (UA), 0.67 (sFlt-1/PlGF), 0.66 (Cysc), 0.65 (GlyFn/PlGF), 0.64 (PAPP-A2/PlGF), 0.63 (BUN), 0.63 (Cre), and 0.60 (PAPP-A2). With the cut-off values obtained from the ROC analyses, the positive predictive values of these serum markers were between 33.1% and 58.5%, and the negative predictive values were between 80.9% and 89.5%. Conclusions: Further studies are warranted to confirm the clinical utilities of the serum markers in preeclampsia prediction

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Predictive values of multiple serum biomarkers in women with suspected preeclampsia: a prospective study

10.21203/rs.3.rs-33584/v1 ◽

2020 ◽

Author(s):

Jing Wang ◽

Honghai Hu ◽

Xiaowei Liu ◽

Shenglong Zhao ◽

Yuanyuan Zheng ◽

...

Keyword(s):

Medical Records ◽

Serum Levels ◽

Serum Markers ◽

Serum Biomarkers ◽

Serum Samples ◽

Predictive Values ◽

Independent Risk Factors ◽

A Prospective Study ◽

In Pregnancy

Abstract Background Early preeclampsia (PE) prediction has been shown to improve the maternal and fetal outcomes in pregnancy. We aimed to evaluate the PE prediction values of a series of serum biomarkers. Methods The singleton pregnant women with PE-related clinical and/or laboratory presentations were recruited and had the blood drawn at their first visits. The prospective cohort was further divided into the PE-positive and PE-negative groups based on the follow-up results. The following markers were tested with the collected serum samples: sFlt-1, PlGF, M, tPAI-C, compliment factors C1q, B, H, BUN, GlyFn, PAPP-A2, BUN, Cre, UA and Cysc. Results Totally 196 women suspected for PE were recruited with follow-up medical records. Twenty-five percent of the recruited subjects developed PE before delivery and 75% remained PE-negative. The serum levels of sFlt-1, BUN, Cre, UA, Cysc and PAPP-A2 were significantly elevated and the PlGF was significantly decreased in the PE-positive patients. The AUCs were listed in the order of decreasing values: UA (AUC = 0.73), sFlt-1/PlGF (AUC = 0.67), Cysc (AUC = 0.66), GlyFn/PlGF (AUC = 0.65), PlGF (AUC = 0.64), PAPP-A2/PlGF (AUC = 0.64), sFlt-1 (AUC = 0.63), BUN (AUC = 0.63), Cre (AUC = 0.63), and PAPP-A2 (AUC = 0.60) in the ROC analyses. The Logistic regression analysis showed that UA and PAPP-A2 were independent risk factors for PE development with the odds ratios of 3.3 and 2.2 respectively. Moreover, the PPVs of UA and PAPP-A2 were 48.9%, and 40.4%; the NPVs of UA and PAPP-A2 were 82.1% and 81.9%. Conclusions Further studies are warranted to confirm the clinical utilities of the serum markers in PE prediction.

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Long-term predictors of remission in patients treated for medication-overuse headache at a specialized headache center: A prospective cohort study

Cephalalgia ◽

10.1177/0333102416683918 ◽

2016 ◽

Vol 38 (2) ◽

pp. 265-273 ◽

Cited By ~ 9

Author(s):

Jasna J Zidverc-Trajkovic ◽

Tatjana Pekmezovic ◽

Zagorka Jovanovic ◽

Aleksandra Pavlovic ◽

Milija Mijajlovic ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Medication Overuse ◽

Medication Overuse Headache ◽

Predictive Values ◽

One Year ◽

The One

Objective To evaluate long-term predictors of remission in patients with medication-overuse headache (MOH) by prospective cohort study. Background Knowledge regarding long-term predictors of MOH outcome is limited. Methods Two hundred and forty MOH patients recruited from 2000 to 2005 were included in a one-year follow-up study and then subsequently followed until 31 December 2013. The median follow-up was three years (interquartile range, three years). Predictive values of selected variables were assessed by the Cox proportional hazard regression model. Results At the end of follow-up, 102 (42.5%) patients were in remission. The most important predictors of remission were lower number of headache days per month before the one-year follow-up (HR-hazard ratio = 0.936, 95% confidence interval (CI) 0.884–0.990, p = 0.021) and efficient initial drug withdrawal (HR = 0.136, 95% CI 0.042–0.444, p = 0.001). Refractory MOH was observed in seven (2.9%) and MOH relapse in 131 patients (54.6%). Conclusions Outcome at the one-year follow-up is a reliable predictor of MOH long-term remission.

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Global Longitudinal Strain in Heart Transplantation Recipients Using Different Vendors: Reliability and Validity in a Tertiary Hospital in Colombia.

10.21203/rs.3.rs-357760/v1 ◽

2021 ◽

Author(s):

Oscar Mauricio Perez Fernandez ◽

Hector M. Medina ◽

Mónica López ◽

Madeleine Barrera ◽

Azucena Martinez ◽

...

Keyword(s):

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Intraclass Correlation ◽

Reliability And Validity ◽

Roc Curves ◽

Tertiary Hospital ◽

Operating Characteristics ◽

Predictive Values ◽

Left Ventricle Function

Abstract Global Longitudinal Strain (GLS) is a useful tool to follow-up heart transplant (HT) recipients. Important inter-vendor variability of GLS measurements has been reported in healthy subjects and different conditions, but there is still limited evidence among HT patients. We assessed the reliability and validity of GLS using two vendors (General Electric and Philips) in a group of consecutive and stable adult HT recipients. Patients underwent two concurrent GLS analyses during their echocardiographic follow-up. We evaluated GLS inter-vendor reliability using Bland-Altman’s limits of agreement (LOA) plots, computing its coverage probability (CP) and the intraclass correlation coefficient (ICC). Validity was assessed though receiver operating characteristics (ROC) curves, predictive values, sensitivity and specificity of GLS for each vendor to detect a normal left ventricle function. 78 pairs of GLS studies in 53 stable HT patients were analyzed. We observed a modest inter-vendor reliability with a broad LOA (less than 50% of values falling out our CP of 2% and an ICC of 0.49). ROC analyses (areas under the curve of 0.824 Vs. 0.631, p<0.05) and diagnosis test indices (Sensitivity of 0.73 Vs. 0.64; and Specificity of 0.79 Vs. 0.50) favored GE over Philips. Inter-vendor variability for GLS analysis exceeded clinically acceptable limits in HT recipients. GLS from GE software seemed to show higher validity as compared to Philips’. The present study provides evidence to consider caution for the interpretation of GLS for clinical management in the follow-up of HT patients, especially when GLS is measured by different vendors.

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Risk assessment of preterm birth through identification and stratification of pregnancies using a real-time scoring algorithm

SAGE Open Medicine ◽

10.1177/2050312120986729 ◽

2021 ◽

Vol 9 ◽

pp. 205031212098672

Author(s):

Lisa BE Shields ◽

Clayton Weymouth ◽

Kevin L Bramer ◽

Scott Robinson ◽

Donna McGee ◽

...

Keyword(s):

Preterm Birth ◽

Pregnant Women ◽

Real Time ◽

First Trimester ◽

Operating Characteristics ◽

Early Care ◽

Likelihood Ratios ◽

Third Trimester ◽

Predictive Values ◽

Scoring Algorithm

Introduction: Preterm birth poses a significant challenge. This study evaluated a real-time scoring algorithm to identify and stratify pregnancies to indicate preterm birth. Methods: All claims data of pregnant women were reviewed between 1 January 2014 and 31 October 2018 in Kentucky. Results: A total of 29,166 unique women who were matched to a live newborn were documented, with the pregnancy identified during the first trimester in 54.1% of women. Negative predictive values, sensitivity, and positive likelihood ratios increased from the first to third trimesters as pregnant women who were matched to a live newborn had more visits with their physicians. The area under the receiving-operating characteristics curve on test data classifying preterm birth was 0.59 for pregnancies identified during the first trimester, 0.62 for pregnancies identified in the second trimester, and 0.73 for pregnancies identified in the third trimester. Conclusions: This study presents a real-time scoring algorithm of indicating preterm birth in the first trimester of gestation which permits stratification of pregnancies to provide more efficient early care management.

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Development and validation of the OUTCoV score to predict the risk of hospitalisation among patients with SARS-CoV-2 infection in ambulatory settings: a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2020-044242 ◽

2021 ◽

Vol 11 (6) ◽

pp. e044242

Author(s):

Frederique Jacquerioz ◽

Stéphanie Baggio ◽

Angele Gayet-Ageron ◽

François Chappuis ◽

Laurent Getaz ◽

...

Keyword(s):

Cohort Study ◽

Prediction Model ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

University Hospital ◽

Ambulatory Setting ◽

Likelihood Ratios ◽

Predictive Values ◽

Rule Out

ObjectivesTo develop and validate a rule-out prediction model for the risk of hospitalisation among patients with SARS-CoV-2 infection in the ambulatory setting to derive a simple score to determine outpatient follow-up.DesignProspective cohort study.SettingSwiss university hospital.Participants1459 individuals with a positive result for SARS-CoV-2 infection between 2 March and 23 April 2020.MethodsWe applied the rule of 10 events per variable to construct our multivariable model and included a maximum of eight covariates. We assessed the model performance in terms of discrimination and calibration and performed internal validation to estimate the statistical optimism of the final model. The final prediction model included age, fever, dyspnoea, hypertension and chronic respiratory disease. To develop the OUTCoV score, we assigned points for each predictor that were proportional to the coefficients of the regression equation. Sensitivity, specificity, positive and negative likelihood ratios were estimated, including positive and negative predictive values in different thresholds.Main outcome measureThe primary outcome was COVID-19-related hospitalisation.ResultsThe OUTCoV score ranged from 0 to 7.5 points. The two threshold parameters with optimal rule-out and rule-in characteristics for the risk of hospitalisation were 3 and 5.5, respectively. Outpatients with a score <3 (997/1459; 68.3%) had no follow-up as at low risk of hospitalisation (1.8%; 95% CI 1.1 to 2.8). For a score ≥5.5 (20/1459; 1.4%), the hospitalisation risk was higher (30%; 95% CI 11.9 to 54.3).ConclusionsThe OUTCoV score allows to rule out two-thirds of outpatients with SARS-CoV-2 infection presenting a low hospitalisation risk and to identify those at high risk that require careful follow-up to assess the need for hospitalisation. The model provides a simple decision-making tool for an effective allocation of resources to maintain quality care for outpatient populations.

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Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2021-049559 ◽

2021 ◽

Vol 11 (11) ◽

pp. e049559

Author(s):

Lilja Thorgeirsdottir ◽

Malin Andersson ◽

Ove Karlsson ◽

Sven-Egron Thörn ◽

Jonatan Oras ◽

...

Keyword(s):

Cohort Study ◽

Pregnant Women ◽

Objective Assessment ◽

Psychological Impact ◽

Routine Data ◽

Personal Identification ◽

University Hospital ◽

Ethical Review ◽

Multisystem Disorder

IntroductionPre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care.Methods and analysisThis is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up.Ethics and disseminationBy creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals.Trial registration numberISRCTN13060768

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Evaluation of Maternal Serum sHLA-G Levels for Trisomy 18 Fetuses Screening at Second Trimester

Frontiers in Genetics ◽

10.3389/fgene.2020.497264 ◽

2021 ◽

Vol 11 ◽

Author(s):

Danping Xu ◽

Yiyang Zhu ◽

Lanfang Li ◽

Yingping Xu ◽

Weihua Yan ◽

...

Keyword(s):

Pregnant Women ◽

Prenatal Screening ◽

Maternal Serum ◽

Trisomy 18 ◽

Second Trimester ◽

Serum Samples ◽

Predictive Values ◽

Second Trimester Screening ◽

Β Hcg ◽

Screening Marker

Human leukocyte antigen-G (HLA-G) has been widely acknowledged to play critical roles in fetal-maternal maintenance. However, the significance of using maternal serum sHLA-G to detect prenatal chromosomal abnormality has not been investigated. In China, prenatal screening using maternal α-fetoprotein (AFP), unconjugated estriol (uE3), and free β subunit human chorionic gonadotropin (β-hCG) in the second trimester has been widely applied. In this study, we evaluated the use of sHLA-G as a screening marker, compared with traditional second trimester prenatal screening. Serum samples from 1,019 singleton women in their second trimester were assessed. Among them, 139 infants were confirmed with trisomy 21 (T21) by karyotyping, 83 were confirmed with trisomy 18 (T18), and the remaining 797 infants had no abnormalities. The sHLA-G levels in maternal sera were significantly lower in pregnant women with T18 fetuses (median: 47.8 U/ml, range: 9.8–234.2 U/ml) and significantly higher in those with T21 fetuses (median: 125.7 U/ml, range: 28.7–831.7 U/ml), compared with the normal controls (median: 106.3 U/ml, range: 50.5–1136.4 U/ml) (p < 0.001). The risk values of the screening of T21 or T18 fetuses were assessed using mean and standard deviation log10 analyte multiples of median (MoM) which showed that the predictive values of sHLA-G were the same as free β-hCG, and superior to AFP and uE3 for T18 screening. Logistic regression analysis revealed that sHLA-G MoM was the highest risk factor associated with pregnant women carrying T18 fetuses [Exp(B): 171.26, 95% CI: 36.30–807.97, p < 0.001]. Receiver operating characteristic (ROC) analysis revealed that the area under ROC curve for sHLA-G MoM was 0.915 (95% CI, 0.871–0.959, p < 0.001), for AFP MoM was 0.796 (95% CI, 0.730–0.861, p < 0.001), for free β-hCG MoM was 0.881 (95% CI, 0.829–0.934, p < 0.001), and for uE3 MoM was 0.876 (95% CI, 0.828–0.923, p < 0.001) in the T18 group. sHLA-G MoM demonstrated the best sensitivity and negative predictive value. For the first time, our findings reveal that sHLA-G is a better second trimester screening marker for the detection of T18 fetuses and the combined application of sHLA-G with AFP, free β-hCG, and uE3 could improve clinical screening for T18 fetuses.

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Steroidomics for highlighting novel serum biomarkers of testosterone doping

Bioanalysis ◽

10.4155/bio-2019-0079 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1169-1185 ◽

Cited By ~ 11

Author(s):

Federico Ponzetto ◽

Julien Boccard ◽

Raul Nicoli ◽

Tiia Kuuranne ◽

Martial Saugy ◽

...

Keyword(s):

High Performance ◽

Biomarker Discovery ◽

High Resolution Mass Spectrometry ◽

Serum Markers ◽

Serum Biomarkers ◽

Serum Samples ◽

Steroid Profiling ◽

Efficient Alternative ◽

Detection Capabilities ◽

Endogenous Steroid

Aim: Quantification of testosterone (T) and 5α-dihydrotestosterone serum concentrations proved to be an efficient alternative to urinary steroid profiling for the detection of T doping. In this context, additional serum markers could be discovered by exploratory untargeted steroidomics studies. Results: Endogenous steroid metabolites were monitored by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry in serum samples collected during a T administration clinical trial. A three-step workflow for accurate review of annotation was used and multifactorial data analysis allowed highlighting promising serum biomarkers. Longitudinal monitoring of selected compounds was performed to assess T abuse detection capabilities. Conclusion: Application of serum steroidomics showed high potential for biomarker discovery of T doping, suggesting longitudinal monitoring of steroid hormones in serum as a significant improvement in detection of endogenous steroids abuse.

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