Early Prediction Of Preeclampsia Research Articles

Maternal angiogenic factor disruptions prior to clinical diagnosis of preeclampsia: insights from the REVAMP study.

Preeclampsia is characterized by impaired angiogenesis and assessment of angiogenic factors can play a crucial role in the early diagnosis of preeclampsia. The current study reports the levels of angiogenic factors longitudinally from early pregnancy in women with preeclampsia and in the subtypes of preeclampsia, to identify their role in early prediction of preeclampsia. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from 2 hospitals. Blood samples were collected, plasma samples were separated and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery. The current study includes a total of 108 women developed preeclampsia (PE), and 216 matched controls. Angiogenic factors were estimated using commercially available ELISA kits. Receiver operating characteristic (ROC) curves were used to evaluate the potential diagnostic value in the prediction of PE. Lower levels of VEGF, PlGF, and higher levels of sEng and sEng/PlGF ratio (p < 0.05 for all) predate clinical diagnosis in women with preeclampsia. sEng levels and sEng/PlGF ratio showed significant correlation with odds of preeclampsia at all the timepoints. This study identifies a cut off of 33.5 for sFlt-1/PlGF and 25.9 for sEng/PlGF for prediction of early onset preeclampsia. This study reports various angiogenic factors serially across gestation in a general population to identify women at risk of developing preeclampsia and its subtypes. The study also reports a potential biomarker and a pragmatic window for estimation of angiogenic markers to identify women at risk.

The role of cell-free DNA biomarkers and patient data in the early prediction of preeclampsia: an artificial intelligence model

ObjectiveAccurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12-16 weeks’ gestation when there is evidence for its effectiveness, as well as guiding appropriate pregnancy care pathways and surveillance. The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks’ gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA (cfDNA) screening. Secondary outcomes were prediction of early onset preeclampsia (<34 weeks’ gestation) and term preeclampsia (≥37 weeks’ gestation). MethodsThis secondary analysis of a prospective, multicenter, observational prenatal cfDNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and two characteristics of cfDNA, total cfDNA and fetal fraction (FF), were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the ‘reference’ classifier was a shallow logistic regression (LR) model. We also explored several feedforward (non-linear) neural network (NN) architectures with one or more hidden layers and compared their performance with the LR model. We selected a simple NN model built with one hidden layer and made up of 15 units. ResultsOf 17,520 participants included in the final analysis, 72 (0.4%) developed early onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cfDNA measurement was 12.6 weeks and 2,155 (12.3%) had their cfDNA measurement at 16 weeks’ gestation or greater. Preeclampsia was associated with higher total cfDNA (median 362.3 versus 339.0 copies/ml cfDNA; p<0.001) and lower FF (median 7.5% versus 9.4%; p<0.001). The expected, cross-validated area under the curve (AUC) scores for early onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively for the LR model, and 0.797, 0.800, and 0.713, respectively for the NN model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% CI 0.569, 0.599) for the LR model and 59.3% (95% CI 0.578, 0.608) for the NN model.The contribution of both total cfDNA and FF to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cfDNA and FF features from the NN model was associated with a 6.9% decrease in sensitivity at a 15% screen positive rate, from 54.9% (95% CI 52.9-56.9) to 48.0% (95% CI 45.0-51.0). ConclusionRoutinely available patient characteristics and cfDNA markers can be used to predict preeclampsia with performance comparable to other patient characteristic models for the prediction of preterm preeclampsia. Both LR and NN models showed similar performance.

Prediction of preeclampsia from retinal fundus images via deep learning in singleton pregnancies: a prospective cohort study.

Early prediction of preeclampsia (PE) is of universal importance in controlling the disease process. Our study aimed to assess the feasibility of using retinal fundus images to predict preeclampsia via deep learning in singleton pregnancies. This prospective cohort study was conducted at Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine. Eligible participants included singleton pregnancies who presented for prenatal visits before 14 weeks of gestation from September 1, 2020, to February 1, 2022. Retinal fundus images were obtained using a nonmydriatic digital retinal camera during their initial prenatal visit upon admission before 20 weeks of gestation. In addition, we generated fundus scores, which indicated the predictive value of hypertension, using a hypertension detection model. To evaluate the predictive value of the retinal fundus image-based deep learning algorithm for preeclampsia, we conducted stratified analyses and measured the area under the curve (AUC), sensitivity, and specificity. We then conducted sensitivity analyses for validation. Our study analyzed a total of 1138 women, 92 pregnancies developed into hypertension disorders of pregnancy (HDP), including 26 cases of gestational hypertension and 66 cases of preeclampsia. The adjusted odds ratio (aOR) of the fundus scores was 2.582 (95% CI, 1.883-3.616; P < 0.001). Otherwise, in the categories of prepregnancy BMI less than 28.0 and at least 28.0, the aORs were 3.073 (95%CI, 2.265-4.244; P < 0.001) and 5.866 (95% CI, 3.292-11.531; P < 0.001). In the categories of maternal age less than 35.0 and at least 35.0, the aORs were 2.845 (95% CI, 1.854-4.463; P < 0.001) and 2.884 (95% CI, 1.794-4.942; P < 0.001). The AUC of the fundus score combined with risk factors was 0.883 (sensitivity, 0.722; specificity, 0.934; 95% CI, 0.834-0.932) for predicting preeclampsia. Our study demonstrates that the use of deep learning algorithm-based retinal fundus images offers promising predictive value for the early detection of preeclampsia.

Maternal Serum Activin A, Inhibin A and Follistatin-Related Proteins across Preeclampsia: Insights into Their Role in Pathogenesis and Prediction.

Within the endocrine-paracrine signalling network at the maternal-foetal interface, the activin-inhibin-follistatin system modulates extravillous trophoblast invasion, suggesting a potential role in preeclampsia pathogenesis. This study aimed to compile the evidence published in the last decade regarding the variation in maternal serum activins, inhibin- and follistatin-related proteins in preeclamptic pregnancies compared to healthy pregnancies, and to discuss their role in predicting and understanding the pathophysiology of preeclampsia. A scoping review was conducted in MEDLINE, EMBASE and LILACS databases to identify studies published within the last ten years (2012-2022). Thirty studies were included. None of the studies addressed maternal serum changes of isoforms different from activin A, inhibin A, follistatin, and follistatin-like 3. Sixteen studies evaluated the potential of these isoforms in predicting preeclampsia through the area under the curve from a receiver operating characteristic curve. In preeclampsia, inhibin A is upregulated in all trimesters, whereas activin A increases exclusively in the late second and third trimesters. Serum follistatin levels are reduced in women with preeclampsia during the late second and third trimesters. However, changes in follistatin-like 3 remain inconclusive. Inhibin A and activin A can potentially serve as biomarkers of early-onset preeclampsia based on the outcomes of the receiver operating characteristic curve analysis. Further investigations are encouraged to explore the feasibility of quantifying maternal serum levels of activin A and inhibin A as a clinical tool in early preeclampsia prediction.

Development of a Urine Metabolomics Biomarker-Based Prediction Model for Preeclampsia during Early Pregnancy

Preeclampsia (PE) is a condition that poses a significant risk of maternal mortality and multiple organ failure during pregnancy. Early prediction of PE can enable timely surveillance and interventions, such as low-dose aspirin administration. In this study, conducted at Stanford Health Care, we examined a cohort of 60 pregnant women and collected 478 urine samples between gestational weeks 8 and 20 for comprehensive metabolomic profiling. By employing liquid chromatography mass spectrometry (LCMS/MS), we identified the structures of seven out of 26 metabolomics biomarkers detected. Utilizing the XGBoost algorithm, we developed a predictive model based on these seven metabolomics biomarkers to identify individuals at risk of developing PE. The performance of the model was evaluated using 10-fold cross-validation, yielding an area under the receiver operating characteristic curve of 0.856. Our findings suggest that measuring urinary metabolomics biomarkers offers a noninvasive approach to assess the risk of PE prior to its onset.

A Study on Sensitivity of Angiogenic Factors as Predictors of Preeclampsia and Role of Aspirin in Preventing Preterm Preeclampsia

Background Preeclampsia is one of the hypertensive disorders of pregnancy causing maternal and perinatal mortality and morbidity. The global burden of Pre-eclampsia and eclampsia is 5-10. The prevalence of preeclampsia-complicating pregnancy in India is 7.8. Early prediction of preeclampsia and prophylactic use of aspirin reduces morbidity and mortality.Objectives To study the role of angiogenic factors and biophysical markers to identify women at high risk for developing preterm preeclampsia. To study the diagnostic value of angiogenic factors as predictors of preterm preeclampsia in early pregnancy. To compare the benefits of prophylactic use of 150mg of Aspirin versus 75mg of Aspirin from 11-16 weeks of gestation in reducing the incidences of preterm preeclampsia.Methods It was a two year study conducted at Rajarajeswari Medical College and Hospital. Data for the study was collected from women attending antenatal clinics at 11 weeks 0days to 13weeks 6days after taking informed consent. Screening for preeclampsia was done using biophysical and biochemical tests. Screen-positive women were grouped randomly into Group A and Group B. They were given 7mg and 150mg aspirin and maternal and fetal outcome was analysed.Results In our study 489.6 women were screened positive for preeclampsia. There were no significant differences between the 75mg aspirin group and the 150mg aspirin group with regard to demographic characteristics. Pre-eclampsia occurred in 27.2 of participants in the 75mg aspirin group compared with 4.1 in the 150 mg aspirin group. There was a significant difference in the incidence of PE p0.0293 its severity and the period of gestation at delivery in the two groups. The positive predictive value of the screening method in our study is 12.7 and the negative predictive value is 91.6.Conclusion Our study showed that screening test was beneficial in identifying high-risk cases but the study population was very less. Early screening and use of prophylactic aspirin reduce the development preterm preeclampsia. Aspirin is a safe economical and easily available drug.

Mendelian randomization study reveals a causal relationship between rheumatoid arthritis and risk for pre-eclampsia.

Epidemiological observational studies have investigated the relationship between rheumatoid arthritis(RA) and pre-eclampsia, but no consistent conclusions were obtained due to various limitations. Hence, we conducted a two-sample mendelian randomization analysis to evaluate the potential causal effect of RA on pre-eclampsia. Summary-level statistics for RA were derived from a large-scale meta-analysis of datasets of genome-wide association studies(GWAS) which involved 14,361 cases and 43,923 controls. Moreover, summary statistics for pre-eclampsia or eclampsia were sourced from the Finn biobank which contained 3,903 cases and 114,735 controls. The inverse variance weighting (IVW) as well as other four effective methods including MR-Egger, weighted median, weighted mode, and simple mode were applied to deduce the potential causal relationships between RA and pre-eclampsia comprehensively. The two-sample MR analysis suggested a strong causal relationship between RA and pre-eclampsia[OR,1.05;95%CI, 1.01-1.09;p<0.05]. The OR estimates obtained from the weighted mode[OR,1.09;95%CI,1.03-1.15;p<0.01] and weighted median[OR,1.07;95%CI, 1.01-1.14;p<0.05] were similar to those from the IVW method, but there was no significant association observed in MR Egger and simple mode analysis. This MR analysis provides evidence of a positive causal association between RA and pre-eclampsia genetically. Our findings highlight the importance of more intensive prenatal care and early intervention among pregnant women with RA to prevent potential adverse obstetric outcomes. Moreover, our study provides clues for risk factor identification and early prediction of pre-eclampsia.

Investigation of serum enzyme activities and oxidative stress markers in preeclampsia: a multiparameter analysis.

Preeclampsia, a high cause of fetomaternal morbidity-mortality, remains a significant burden affecting 8% of all pregnancies. Environmental conditions induce disease development leading to endothelial dysfunction in genetically predisposed women. Our aim is to discuss oxidative stress as a well-established contributing factor to disease progression with being the first study to show new evidence about serum dehydrogenase enzyme levels (isocitrate, malate, glutamate dehydrogenase) with oxidative markers (myeloperoxidase, total antioxidant-oxidant status, oxidative stress index). Serum parameters were analyzed with photometric method (Abbott ARCHITECT c8000). The enzyme levels and oxidative markers were significantly higher in patients, supporting the redox imbalance in preeclampsia. According to ROC analysis, malate dehydrogenase showed an outstanding diagnostic ability with the highest AUC value of 0.9 and the cut-off value of 51.2 IU/L. Discriminant analysis including malate, isocitrate and glutamate dehydrogenase had predicted preeclampsia with an overall 87.9% accuracy. Considering the above results, we propose that the enzyme levels increase with oxidative stress functioning as antioxidant defense factors. The unique finding of the study is that the serum levels of malate, isocitrate and glutamate dehydrogenase can be used both separately and combined in the early prediction of preeclampsia. As a novel approach, we also offer combining serum isocitrate and glutamate dehydrogenase levels with ALT, AST tests to state liver functions more reliably in patients. Still, larger sample-sized studies investigating enzyme expression levels are required to confirm the recent findings and to reveal underlying mechanisms.

Announcing the winner of the John J. Sciarra IJGO Prize Paper Award for 2021

The editors of the International Journal of Gynecology & Obstetrics (IJGO) are pleased to announce the winner of the prize paper award for the best clinical research paper from a low- or middle-income country published in IJGO during 2021. The winning paper is: Tang X, Guo C, Liu S, Guo J, Hua K and Qiu J. A novel prognostic nomogram utilizing the 2018 FIGO staging system for cervical cancer: A large multicenter study. Int J Gynecol Obstet 2021;155:86–94. https://doi.org/10.1002/ijgo.13644. It was published in the October 2021 issue of IJGO. This award brings with it a stipend of £800, a certificate of recognition, and complimentary access to IJGO for a period of 1 year from the date the prize is awarded. All clinical research articles submitted to the IJGO from low- and middle-income countries that were published in 2021 were considered for this prize. The paper was chosen from 95 qualifying articles. Selection and review were undertaken by the editors, and the Editorial Board of IJGO endorsed the decision. The winning paper by Tang et al. evaluated the prognostic performance of the revised 2018 FIGO staging system for cervical cancer in a multicentre study across four sites. In 3238 patients with cervical cancer, 1841 (almost 60%) were re-staged. Almost one third of these were re-staged due to tumor size, approximately 30% due to lymph node metastasis, and one third due to the inconsistency between the pre-operative and post-operative assessments. They concluded that the 2018 FIGO staging system was a better reflection of the survival of cervical cancer patients. This very important work also allowed the group to establish a nomogram that allowed them to predict the prognosis of cervical cancer more accurately. Additional papers that are worthy of special recognition are awarded an honorable mention. While the honorable mention recognition does not include a financial award, each author receives a certificate of recognition and a letter of commendation from the editors of IJGO. The IJGO Prize Paper Award was established in 1998 for the purpose of encouraging investigators, especially young scientists, from low- and middle-income countries to submit their best clinical research articles for publication in the journal. IJGO is the official publication of FIGO (International Federation of Gynecology and Obstetrics), the primary international organization for the specialty of obstetrics and gynecology. FIGO is dedicated to enhancing the health care of women worldwide. HONORABLE MENTIONS 2021 The following 11 papers receive an honorable mention: China Li Y, Wang H, Zhang Y, et al. Correlation between multi-type human papillomavirus infections and viral loads and the cervical pathological grade. Int J Gynecol Obstet. 2020;152:96–102. https://doi.org/10.1002/ijgo.13406 Wang X, Zhang C, Li X, Qi H, Liu Q, Lei J. Safety and efficacy of titrated oral misoprostol solution versus vaginal dinoprostone for induction of labor: a single-center randomized control trial. Int J Gynecol Obstet. 2021;154:436–443. https://doi.org/10.1002/ijgo.13546 Brazil Laporte M, Becerra A, Castro L, Veiga N Jr, Espejo-Arce X, Bahamondes L. Evaluation of clinical performance when intrauterine devices are inserted by different categories of healthcare professional. Int J Gynecol Obstet. 2021;152:196–201. https://doi.org/10.1002/ijgo.13396 Barbieri MM, Herculano TB, Dantas Silva A, Bahamondes L, Juliato CRT, Surita FG. Acceptability of ENG-releasing subdermal implants among postpartum Brazilian young women during the COVID-19 pandemic. Int J Gynecol Obstet. 2021;154:106–112. https://doi.org/10.1002/ijgo.13663 Turkey Karakas LA, Atilgan AO, Akilli H, Kuscu UE, Haberal A, Ayhan A. Nulliparity and postmenopausal status are independent factors of malignancy potential of endometrial intraepithelial neoplasia in polyps. Int J Gynecol Obstet. 2021;152:433–438. https://doi.org/10.1002/ijgo.13448 Iran Ghotbizadeh Vhdani F, Nasiri Khormoji N, Eftekhar N, et al. A double-blind randomized trial on subendometrial injection of vasopressin to control bleeding in postpartum hysterectomy due to abnormally invasive placenta. Int J Gynecol Obstet. 2021;153:228–233. https://doi.org/10.1002/ijgo.13440 South Africa Budhram S, Vannevel V, Botha T, et al. Maternal characteristics and pregnancy outcomes of hospitalized pregnant women with SARS-CoV-2 infection in South Africa: An International Network of Obstetric Survey Systems-based cohort study. Int J Gynecol Obstet. 2021;155:455–465. https://doi.org/10.1002/ijgo.13917 Goldman B, Naidoo T. Formal training in cardiotocograph interpretation of healthcare practitioners improves interpretation: a prospective descriptive analytical study in a resource constrained setting. Int J Gynecol Obstet. 2021;153:527–532. https://doi.org/10.1002/ijgo.13513 Kenya Gwako GN, Obimbo MM, Gichangi PB, Kinuthia J, Gachuno OW, Were F. Association between obstetric and medical risk factors and stillbirths in a low-income urban setting. Int J Gynecol Obstet. 2021;154:331–336. https://doi.org/10.1002/ijgo.13528 Egypt Abdallah A, Khairy M, Tawfik M, et al. Role of first-trimester three-dimensional (3D) power Doppler of placental blood flow and 3D placental volume in early prediction of pre-eclampsia. Int J Gynecol Obstet. 2021;154:466–473. https://doi.org/10.1002/ijgo.13572 Malaysia Goh YP, Tan PC, Hong JGS, Sulaiman S, Omar, SZ. Combined massage and warm compress to the perineum during active second stage of labor in nulliparas: a randomized trial. Int J Gynecol Obstet. 2021;155:532–538. https://doi.org/10.1002/ijgo.13613

Potential biomarkers and molecular mechanisms in preeclampsia progression.

This study aimed to explore potential biomarkers and molecular mechanisms in preeclampsia (PE) progression. Gene expression profiles of GSE147776 and GSE96984 were downloaded, followed by the identification of common differentially expressed genes (co-DEGs) and common differentially expressed lncRNAs (co-DElncRNAs) in PE patients between the two datasets. Key genes were identified using gene set enrichment analysis (GSEA), followed by functional enrichment analyses. Subsequently, the miRNAs of key genes and miRNA-related lncRNAs were predicted, followed by the construction of the lncRNA–miRNA–gene ceRNA network. Furthermore, the key genes associated with different gestational stages were identified. As a result, 192 co-DEGs and 16 co-DElncRNAs were revealed from the two datasets. Based on two outstanding PE-associated pathways, including glaucoma and PE, identified by GSEA, ten key genes, including IGFBP1, CORIN, and C3, were revealed. Key genes, including IL1A and IL1B, were enriched in the developmental process involved in reproduction. Furthermore, ceRNAs, such as LINC00473-miR-4476-IL1A, LINC00473-miR-1291-IL1B, and NAV2-AS4-miR-6131-REN, were identified. Moreover, REN expression was significantly upregulated in the first- and second-trimester placentae compared to C-section-term placentae. In conclusion, these key genes may serve as novel biomarkers for PE. The detection of REN expression may help in the early prediction of PE and the initiation of prophylactic medical treatment.

Comparison between placental 3D power Doppler and uterine artery pulsatility index in early prediction of pre-eclampsia

Aim of the work: To compare between placental 3D Power Doppler vascular indices and uterine artery pulsatility index in early prediction of preeclampsia. Methods: The prospective comparative observational cohort study included 200 women in their first trimester at 11–14 weeks of pregnancy divided into 2 groups. 100 women with no risk factor to develop preeclampsia (control group), 100 women with any risk factor to develop preeclampsia (case group). All women were examined by 3D abdominal ultrasound, Blood flow in placenta was examined using 3D power Doppler technique for the placental vascular indices. Uterine artery pulsatility index was also assessed. All Patients were followed up to the end of their pregnancies and their medical files reviewed to obtain whether patients developed preeclampsia and other hypertensive disorders. Results: Overall, 17 women developed pre-eclampsia while 183 women remained normotensive (7 out of 100 women in the control group and 10 out of 100 women in the case group). In both groups the women with pre-eclampsia had significantly lower placental vascular indices (vascularization-index, flow index, and vascularization flow index) compared with the normotensive women. In contrast, women with pre-eclampsia in both groups had significantly high mean uterine pulsatility index compared with the normotensive women.

A Study on the Role of Urinary Congophilia in Early Detection of Preeclampsia

Introduction Preeclampsia and eclampsia are important causes of maternal morbidity. Preeclapmtic women secrete misfolded proteins in the urine. Buhimschi et al had developed a new test for diagnosis of preeclampsia. This test is based on staining of misfolded protein with Congo red dye. Misfolded proteins are derived from syncytiotrophoblast microparticles (STBMs). These STBM are membrane bound vesicles and contain misfolded proteins. In preeclampsia, glomeruli of kidneys are disrupted and these damaged protein reach the urine. Aim and Objective This study aimed to investigate the role of urinary congophilia in early prediction of preeclampsia. Materials and Methods This test was done in 250 pregnant women attending the Gynaecological Outpatient Department. Urine sample of early morning was taken and test was done in the Department of Biochemistry. The included pregnant women were of gestational age between 14 and 18 weeks. The staining of urine with Congo red dye was done and washed with methanol. The retention of dye was interpreted with naked eye. The more retention of dye, the more chances of developing preeclampsia later. The patients were followed-up till delivery. The patents who developed preeclampsia later part of pregnancy were recorded. Mean arterial pressure (MAP) and past history and body mass index were also recorded. Results Out of 250 patients, 30 developed preeclampsia later. A total of 34 patients were having positive urinary congophilia and only 20 patients developed preeclampsia later. MAP more than 90 mm Hg is abnormal but 66.7% of patients who developed preeclampsia had MAP &gt;90 mm Hg. In 16.7% of patients, who developed preeclampsia later, had positive past history of hypertension. In 66.7% of patients, who were positive for urinary congophilia, later developed preeclampsia. Conclusion Preeclampsia and eclampsia are important causes of maternal mortality and morbidity. So, early detection can prevent complications and timely management. Urinary congophilia is one of such test which can help in early prediction of preeclampsia. If it is combined with past maternal history and MAP, it gives more good results. The detection rate is much higher if signs and symptoms of preeclampsia are noticed timely.

Early prediction of preeclampsia in pregnancy with cell-free RNA

Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care1–4. Here we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally5. We find that changes in cfRNA gene expression between normotensive and preeclamptic mothers are marked and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial and immune cell types and tissues that reflect key aspects of preeclampsia physiology6–9, suggest new hypotheses for disease progression and correlate with maternal organ health. This enabled the identification and independent validation of a panel of 18 genes that when measured between 5 and 16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care10,11.

Role of Uterine Artery Doppler at 11-14 Weeks of Pregnancy in Early Prediction of Preeclampsia: A Prospective Cohort Study

Introduction: Doppler ultrasonography, by comparing systolic and diastolic waveforms helps in assessment of uteroplacental circulation. Since preeclampsia has ethnic and geographical variations, it is important to understand the prediction modalities in various populations. Aim: To investigate the role of elevated Pulsatility Index (PI) and presence of diastolic notch using uterine artery doppler in early pregnancy in predicting development of preeclampsia among pregnant women. Materials and Methods: A prospective cohort study was conducted on pregnant females visiting the antenatal clinic or Outpatient Department or admitted in the Department of Obstetrics and Gynaecology at People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India, from November 2019 to October 2021. All cases were subjected to uterine artery doppler study, between 11-14 weeks of pregnancy, to note pulsatility index and diastolic notch. All the participants were then screened periodically during their antenatal visits for development of features of preeclampsia and were followed-up monthly upto 20 weeks, every 15 days upto 32 weeks and then weekly till delivery. Pregnancy outcome were measured in terms of presence or absence of preeclampsia. Data was compiled using Microsoft Excel and analysed using Statistical Package for Social Sciences (SPSS) IBM software version 20.0. Categorical data was expressed as frequency and proportions whereas continuous data was expressed as mean and standard deviation. Results: The present study was conducted on a total of 116 cases with the mean age of 26.75±4.31 years. Out of 116 cases, 26 cases developed preeclampsia. Diastolic notch was present in 17 cases (65.4%) patients with preeclampsia and 23 cases (25.6%) non preeclampsia patients. Pulsatility index of more than 1.71 was noted in 14 cases (53.8%) cases with preeclampsia where as 87 cases (96.7%) with non preeclampsia had pulsatility index of less than 1.71. The specificity of diastolic notch 74.4% where as that of pulsatility Index was 96.7 % and the diagnostic accuracy of diastolic notch 72.4% where as that of pulsatility index was 87.1%. Conclusion: Uterine artery doppler is a promising tool for predicting development of preeclampsia by analysing both PI as well as diastolic notch in uterine artery. Doppler had high overall diagnostic accuracy for preeclampsia.

Early Prediction of Preeclampsia: Serum and Exosomal Biomarkers

Early Prediction of Preeclampsia: Serum and Exosomal Biomarkers

Lack of nitric oxide bioavailability in early pregnancy predisposes to dyslipidemia and surges preeclampsia and fetal growth retardation

Background: Hyperlipidemia has been reported in preeclampsia (PrE) and is linked to poor pregnancy outcome and long-term cardiovascular complications. This study aimed to elucidate the relationship between nitric oxide (NO) and blood lipids levels during normal pregnancy and in NG-nitro-l-arginine methyl ester (L-NAME) - induced preeclampsia before and after magnesium sulphate (MgSO4) therapy and its effect on the pregnancy outcome.Methods: Forty female Wistar rats were divided into four groups: non pregnant (NP) group - non pregnant healthy rats receiving no treatment, control pregnant (Con-P) group - control pregnant rats receiving no treatment, pregnant (PE) group - pregnant animals with untreated PrE, and the pregnant MgSO4 (PE-Mg) group - pregnant animals with PrE- treated with MgSO4. The nitric oxide synthase inhibitor L-NAME was used to induce experimental model of PrE in the PE and the PE-Mg groups. The changes in total NO production, total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL-C), high density lipoproteins (HDL), LDL-C/HDL-C ratio, soluble vascular endothelial growth factor receptor-1 (sVEGFR1) also known as sFlt-1, blood pressure, kidney functions, body weight, and pregnancy outcome were assessed.Results: Decreased NO production in the PE group was associated with elevated TC, TG, LDL-C/HDL-C ratio, hypertension, proteinuria, increased urea, creatinine, and sFlt-1 levels, and poor pregnancy outcome demonstrated by high pup mortality rate and low birth weight. Increased NO production in the PE-Mg group treated with MgSO4 therapy was associated with decreased signs of preeclampsia and hypolipidemia and increased pup viability and birth weight.Conclusions: NO bioavailability is crucial for the homeostasis of the lipid profile in normal pregnancy and the prevention of preeclampsia. Routine periodic assessments of the blood lipid profile and the NO production in the pregnant females may be a helpful tool in early prediction of preeclampsia.

Relevance of Placental protein 13 in combination with Xanthine oxidase activity andAsymmetric dimethylargininein early prediction of Preeclampsia with an evidence of LGALS13 gene promoter variant

Introduction and Aim:Preeclampsia is a pregnancy specific hypertensive disorder and its complications are associated with maternal morbidity and mortality. The intention of the study is to determine early placental and endothelial dysfunction markers in first and second trimesters of pregnancy for the prediction of preeclampsia.&#x0D; Materials and Methods:Study design was prospective which enrolled 268 pregnant women during their first ante-natal visit. Blood samples were analysed for Placental protein13 (PP13), Asymmetric dimethyl arginine (ADMA) by ELISA and Xanthine oxidase (XO) activity by colorimetric assay. On follow-up, 22 subjects developed preeclampsia, 12 had spontaneous abortions and the rest remained normotensive till delivery. PP13 gene, LGALS13 was sequenced in preeclampsia cases to know if any polymorphism was present.&#x0D; Results:Results were analysed by Wilcoxon Signed Ranks test know the level of statistical significance, correlation analysis by Spearman’s correlation and diagnostic performance of the measured parameters was assessed by receivers operating characteristic (ROC) curve. Pregnant women who developed Preeclampsia had low PP13 levels in first trimester and elevated ADMA in second trimester (p&lt;0.001). Gene sequencing of LGALS13 in preeclampsia showed -98C/A SNP at promoter region. ROC curve showed AUC for first trimester PP13 (0.932), second trimester PP13 (0.955) second trimester XO activity (0.967) and second trimester ADMA (1.000).&#x0D; Conclusion: The results suggest that oxidative stress, placental and endothelial dysfunction biomarkers would be helpful for early prediction of preeclampsia.

First Trimester Uterine Artery Doppler in Early prediction of Preeclampsia

First Trimester Uterine Artery Doppler in Early prediction of Preeclampsia

Biomarkers for Early Prediction of Pre-Eclampsia

Biomarkers for Early Prediction of Pre-Eclampsia

The role of resistin in early preeclampsia prediction

Resistin might be involved with general inflammation and endothelial dysfunction observed in preeclampsia. We aimed to investigate longitudinal changes in resistin concentrations during high-risk pregnancies and evaluate their significance in preeclampsia development. Ninety-one patients were recruited at 11–14 weeks of gestation. They were followed towards the end of each trimester and before their deliveries. Of the 91 pregnant women, 21 developed preeclampsia, while 70 women did not develop preeclampsia despite being at risk. Compared to the 1st trimester, resistin concentration significantly increased during the 2nd trimester (p<.001). When women were divided into groups of those who developed preeclampsia and those who did not develop preeclampsia, we noticed a significant difference only in women who did not develop preeclampsia (p<.001). Moreover, resistin concentration in the 1st trimester was statistically higher in women who developed preeclampsia when compared to those who did not develop preeclampsia (p<.001). The analysis of the Receiver Operating Characteristics (ROC) curves indicated that inclusion of triglycerides (TG), high-sensitivity C-reactive protein (CRP), and resistin (AUC = 0.870) improved diagnostic accuracy of the basic model including demographic and clinical parameters (AUC = 0.777) for preeclampsia prediction (p<.05). If the concentration of resistin is high in the 1st trimester, such pregnancy at risk is likely to develop preeclampsia as a complication, indicating that resistin concentration in the 1st trimester might contribute to existing predictive and prognostic models for preeclampsia. A multi-marker model, possibly including also resistin and other clinical, metabolic, and inflammatory parameters, seems to be the best approach in late-onset preeclampsia prediction.