Serum hypoxia-inducible factor-1α and uterine artery Doppler ultrasound during the first trimester for prediction of preeclampsia

AbstractThe objective of this study was to determine the predictive value of serum hypoxia-inducible factor-1α (HIF-1α) combined with uterine artery Doppler in singleton pregnancy during 11–13+6 weeks of gestation for preeclampsia. This prospective observational study was conducted in singleton pregnant women at 11–13+6 weeks of gestation who visited the King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University for antenatal care between February 2019 and May 2020. Serum HIF-1α levels and uterine artery Doppler ultrasound were performed. Pregnancy outcomes were recorded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these tests at the optimal cut-off values were determined to predict preeclampsia. A total of 385 participants were analyzed. Of these, 31 cases had preeclampsia (8.1%), and 6 cases of them had early-onset preeclampsia (1.6%). Preeclamptic women had significantly higher serum HIF-1α levels than normal pregnant women (median 1315.2 pg/ml vs. 699.5 pg/ml, p < 0.001). There was no difference in the mean pulsatility (PI) of the uterine artery. Serum HIF-1α levels were higher than 1.45 multiple of median for the gestational age as a cut-off value for predicting preeclampsia; the sensitivity, specificity, PPV, and NPV were 66.7%, 71.5%, 17.2%, and 96.2%, respectively. When a combination of abnormal serum HIF-1α levels and abnormal uterine artery Doppler PI (above the 95th percentile) were used as a predictive value to predict preeclampsia, the sensitivity, specificity, PPV, and NPV were 74.2%, 67.2%, 16.6%, and 96.8%, respectively. This study showed that the serum HIF-1α levels with or without uterine artery Doppler at 11–13+6 weeks of gestation were effective in predicting preeclampsia.

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Prediction of preeclampsia using a combination of serum micro RNA-210 and uterine artery Doppler ultrasound

Science Progress ◽

10.1177/00368504211036856 ◽

2021 ◽

Vol 104 (3) ◽

pp. 003685042110368

Author(s):

Ananya Trongpisutsak ◽

Vorapong Phupong

Keyword(s):

Pregnant Women ◽

Doppler Ultrasound ◽

Predictive Value ◽

Early Onset ◽

Uterine Artery ◽

Micro Rna ◽

Predictive Values ◽

Uterine Artery Doppler ◽

Early Onset Preeclampsia ◽

Sensitivity Specificity

The objective was to determine whether a combination of serum micro RNA-210 level and uterine artery Doppler can predict preeclampsia in pregnant women at 16–24 weeks gestation. A prospective observational study conducted in singleton pregnant women at 16–24 weeks of gestation who had prenatal care at the King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand between 2017 and 2018. Uterine artery Doppler ultrasound and blood testing for serum micro RNA-210 were performed. Pregnancy outcomes were recorded. Optimal cut-off for uterine artery pulsatility index (PI) and serum micro RNA-210 were obtained to calculate the predictive values for preeclampsia. Data from 443 participants were analyzed. Twenty-two cases developed preeclampsia (5.0%) and seven of these preeclamptic cases had early-onset preeclampsia (1.6%). Pregnant women with preeclampsia had higher mean PI of the uterine artery (1.34 ± 0.52 vs 0.98 ± 0.28, p = 0.004), higher detection rates of diastolic notching (45.5% vs 11.2%, p < 0.001), and lower median serum micro RNA-210 level (22.86 vs 795.78, p < 0.001) than pregnant women without preeclampsia. Using abnormal serum micro RNA-210 level, abnormal mean PI or uterine artery diastolic notches to predict for preeclampsia, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.5%, 54.9%, 10.0%, and 99.6%, respectively. For early-onset preeclampsia prediction, the sensitivity, specificity, PPV, and NPV were 100.0%, 53.2%, 3.3%, and 100.0%, respectively. This study demonstrated that a combination of serum micro RNA-210 and uterine artery Doppler is effective in predicting preeclampsia in the second trimester.

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Maternal Serum EG-VEGF as A First Trimester Predictor of Hypertensive Disorders of Pregnancy: A Prospective Cohort Study

10.21203/rs.3.rs-156363/v1 ◽

2021 ◽

Author(s):

Shiyu Zeng ◽

Ling Yu ◽

Yiling Ding ◽

Mengyuan Yang

Keyword(s):

Cohort Study ◽

Growth Factor ◽

Prediction Model ◽

Pregnant Women ◽

Predictive Value ◽

Prospective Cohort ◽

First Trimester ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Sensitivity Specificity

Abstract Background This study aims to explore whether plasma endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in the first trimester can be used as a predictor of hypertensive disorders of pregnancy (HDP), and compare it with placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to evaluate its prediction of HDP value. Methods This is a prospective cohort study that records the medical history of the pregnant women included in the study at 11–13 weeks’ gestation, and analyzes serum biochemical markers including EG-VEGF, PIGF, sFlt-1 and sFlt-1/PIGF. The predictive values of these tests were determined. We used the receiver operating characteristic (ROC) curve to find the optimal cut-off value for each biomarker and compare the operating characteristics (sensitivity, specificity). Logistic regression analysis was used to create a prediction model for HDP based on maternal characteristics and maternal biochemistry. Results Data were obtained from 205 pregnant women. 17 cases were diagnosed with HDP, the incidence rate was 8.2% (17/205). Women who developed HDP had a significantly higher body mass index (BMI) and mean arterial pressure (MAP). Serum EG-VEGF levels in the first trimester are significantly higher in pregnant women with HDP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of serum EG-VEGF levels more than 227.83 pg/ml for predicting HDP were 43%, 93%, 86% and 62%, respectively. We established a prediction model in the first trimester include maternal BMI, MAP, and EG-VEGF, with an AUC of 0.8861 (95%CI: 0.7905–0.9818), which is better than using EG-VEGF alone (AUC: 0.66). Conclusion This study demonstrated that serum EG-VEGF is a promising biomarker for predicting HDP in the first trimester. It has better predictive performance compared with the currently used biomarkers like PIGF and sFlt-1. Combining maternal clinical characteristics and biochemical tests at 11–13 weeks can effectively identify women at high risk of HDP.

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Significance of obstetric Doppler studies in prediction of perinatal outcome in pregnancy induced hypertension

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20172312 ◽

2017 ◽

Vol 6 (6) ◽

pp. 2354 ◽

Cited By ~ 1

Author(s):

Pradip R. Gaikwad ◽

Manisha R. Gandhewar ◽

Nity Rose ◽

Vidyadhar Suryakar

Keyword(s):

Diagnostic Accuracy ◽

Doppler Ultrasound ◽

Predictive Value ◽

Perinatal Outcome ◽

Uterine Artery ◽

Pregnancy Induced Hypertension ◽

Doppler Studies ◽

Uterine Artery Doppler ◽

Adverse Perinatal Outcome ◽

Induced Hypertension

Background: Pregnancy induced hypertension (PIH) is associated with adverse perinatal outcome. Multi vessel color Doppler studies are useful in these cases for timely intervention. The aim of present study was to know the significance of umbilical, middle cerebral and uterine artery Doppler studies in PIH and to analyse its role in predicting perinatal outcome.Methods: This was a prospective study of 106 singleton pregnancies in the third trimester with PIH. The results of last Doppler ultrasound within one week of delivery were used for analysis. Adverse perinatal outcome was studied in the form of emergency cesarean section for fetal distress, meconium stained amniotic fluid, Apgar at 5 min <7, NICU admission and perinatal mortality (stillbirths and neonatal death). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of various Doppler parameters were calculated after comparing with standard.Results: In the present study specificity and diagnostic accuracy of all Doppler ultrasound parameters was high in predicting adverse perinatal outcome. Cerebroplacental ratio showed highest specificity (98.55%), PPV (94.44%) and diagnostic accuracy (80.19%) in predicting adverse perinatal outcome and it is better than MCA PI and UA PI alone. Uterine artery Doppler evaluation also gives additional information in predicting adverse perinatal outcome.Conclusions: Amongst various Doppler parameters cerebroplacental index (MCA/UA PI) is best predictor of adverse perinatal outcome.

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NIPT Technique Based on the Use of Long Chimeric DNA Reads

Genes ◽

10.3390/genes11060590 ◽

2020 ◽

Vol 11 (6) ◽

pp. 590

Author(s):

Vera Belova ◽

Daria Plakhina ◽

Sergey Evfratov ◽

Kirill Tsukanov ◽

Gennady Khvorykh ◽

...

Keyword(s):

Pregnant Women ◽

Predictive Value ◽

High Performance ◽

High Throughput Sequencing ◽

Prenatal Testing ◽

First Trimester ◽

Extracellular Dna ◽

Trimester Screening ◽

Sensitivity Specificity ◽

Analytical Approaches

Non-invasive prenatal testing (NIPT) for aneuploidy on Chromosomes 21 (T21), 18 (T18) and 13 (T13) is actively used in clinical practice around the world. One of the limitations of the wider implementation of this test is the high cost of the analysis itself, as high-throughput sequencing is still relatively expensive. At the same time, there is an increasing trend in the length of reads yielded by sequencers. Since extracellular DNA is short, in the order of 140–160 bp, it is not possible to effectively use long reads. The authors used high-performance sequencing of cell-free DNA (cfDNA) libraries that went through additional stages of enzymatic fragmentation and random ligation of the resulting products to create long chimeric reads. The authors used a controlled set of samples to analyze a set of cfDNA samples from pregnant women with a high risk of fetus aneuploidy according to the results of the first trimester screening and confirmed by invasive karyotyping of the fetus using laboratory and analytical approaches developed by the authors. They evaluated the sensitivity, specificity, PPV (positive predictive value), and NPV (negative predictive value) of the results. The authors developed a technique for constructing long chimeric reads from short cfDNA fragments and validated the test using a control set of extracellular DNA samples obtained from pregnant women. The obtained sensitivity and specificity parameters of the NIPT developed by the authors corresponded to the approaches proposed earlier (99.93% and 99.14% for T21; 100% and 98.34% for T18; 100% and 99.17% for T13, respectively).

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Evaluation of 7 Serum Biomarkers and Uterine Artery Doppler Ultrasound for First-Trimester Prediction of Preeclampsia: A Systematic Review

Obstetrical & Gynecological Survey ◽

10.1097/ogx.0b013e3182227027 ◽

2011 ◽

Vol 66 (4) ◽

pp. 225-239 ◽

Cited By ~ 118

Author(s):

Sylwia Kuc ◽

Esther J. Wortelboer ◽

Bas B. van Rijn ◽

Arie Franx ◽

Gerard H. A. Visser ◽

...

Keyword(s):

Systematic Review ◽

Doppler Ultrasound ◽

Uterine Artery ◽

First Trimester ◽

Serum Biomarkers ◽

Uterine Artery Doppler

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Effect of Parity on First-Trimester Uterine Artery Doppler Indices and Their Predictive Value for Pregnancy Complications

Gynecologic and Obstetric Investigation ◽

10.1159/000355698 ◽

2014 ◽

Vol 77 (1) ◽

pp. 24-28 ◽

Cited By ~ 1

Author(s):

Banu Dane ◽

Gonca Batmaz ◽

Fulya Ozkal ◽

Zehra Bakar ◽

Cem Dane

Keyword(s):

Pregnancy Complications ◽

Predictive Value ◽

Uterine Artery ◽

First Trimester ◽

Uterine Artery Doppler ◽

Doppler Indices

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The predictive value of 18 and 22 week uterine artery Doppler in patients with low first trimester maternal serum PAPP-A

Prenatal Diagnosis ◽

10.1002/pd.2175 ◽

2009 ◽

Vol 29 (3) ◽

pp. 248-252 ◽

Cited By ~ 7

Author(s):

Stephanie Cooper ◽

Jo-Ann M. Johnson ◽

Amy Metcalfe ◽

Jeffery Pollard ◽

Rebecca Simrose ◽

...

Keyword(s):

Predictive Value ◽

Uterine Artery ◽

First Trimester ◽

Maternal Serum ◽

Uterine Artery Doppler

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Plasma SerpinA5 in conjunction with uterine artery pulsatility index and clinical risk factor for the early prediction of preeclampsia

PLoS ONE ◽

10.1371/journal.pone.0258541 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258541

Author(s):

Yonggang Zhang ◽

Yipeng Zhang ◽

Limin Zhao ◽

Junzhu Shi ◽

Hongling Yang

Keyword(s):

Risk Factor ◽

Doppler Ultrasound ◽

Uterine Artery ◽

Color Doppler ◽

First Trimester ◽

Clinical Risk Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Trophoblastic Cell ◽

Uterine Artery Doppler ◽

Clinical Risk

Object This study aimed to combine plasma protein SerpinA5 with uterine artery doppler ultrasound and clinical risk factor during the first trimester for prediction of preeclampsia. Methods and materials This study was a nested cohort study and was divided into the screening set and developing set. The plasma was collected during the first trimester (11+0–13+6 weeks), at the same time, UtA-PI was detected and recorded with four-dimensional color Doppler ultrasound. These pregnancies were followed up until after delivery. The plasma proteins were examined using ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) and enzyme linked immunosorbent assay (ELISA). Placental samples preserved after delivery were analysed by immunohistochemistry. Clinical risk factors were obtained from medical records or antenatal questionnaires. Upregulation or downregulation of SerpinA5 expression in TEV-1 cells was performed to investigate the role of SerpinA5 in trophoblasts invasion. Results We demonstrated that SerpinA5 levels were greater not only in preeclampsia placental tissue but also in plasma (both p<0.05), and we found that SerpinA5 may interfere with trophoblastic cell invasion by inhibiting MSP. SerpinA5 may be a potential predictor of preeclampsia. What is more, the sensitivity and specificity of predictive power were strengthened when plasma SerpinA5 was combined with UtA-PI and pre-pregnancy BMI & family history of PE for prediction of preeclampsia. Conclusion These findings showed that placenta-derived plasma SerpinA5 may be a novel biomarker for preeclampsia, which together with uterine artery Doppler ultrasound and clinical risk factor can more effectively predict preeclampsia.

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Uterine Artery Doppler Ultrasonography for First Trimester Prediction of Preeclampsia in Individuals at Risk from Low-Resource Settings

Medicina ◽

10.3390/medicina56090428 ◽

2020 ◽

Vol 56 (9) ◽

pp. 428

Author(s):

Mihaela Oancea ◽

Mihaela Grigore ◽

Razvan Ciortea ◽

Doru Diculescu ◽

Diana Bodean ◽

...

Keyword(s):

At Risk ◽

Pregnant Women ◽

Uterine Artery ◽

Doppler Ultrasonography ◽

First Trimester ◽

Prospective Longitudinal Study ◽

Uterine Artery Doppler ◽

Doppler Examination ◽

Non Invasive ◽

Prospective Longitudinal

Background and objectives: The objective of this study was to evaluate the potential of first trimester uterine artery Doppler ultrasonography for the early prediction of preeclampsia (PE), in at-risk pregnant women. Materials and Methods: This was a prospective longitudinal study, including 120 Caucasian pregnant women with risk factors for PE. The potential of pulsatility indexes (PI) and notch was assessed as a tool for preeclampsia screening. Results: Doppler examination of the uterine artery performed early at 11–14 WA allows the detection of pregnancies that will develop PE with a sensitivity of 61.5% and a specificity of 63.8% based on PI analysis. Predictive power increases slightly by adding bilateral notch (sensitivity = 65.4%; specificity = 66%). Conclusions: Uterine artery Doppler examination is an effective non-invasive screening test for the development of PE in pregnancies at risk, particularly appropriate in health systems with limited means of evaluating other biomarkers.

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