Prediction Of Severe Preeclampsia Research Articles

Prediction of severe preeclampsia and intrauterine growth restriction based on serum placental exosome miR-520a-5p levels during the first-trimester.

To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 ℃. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.

A Second Trimester Prediction Algorithm for Early-Onset Hypertensive Disorders of Pregnancy Occurrence and Severity Based on Soluble fms-like Tyrosine Kinase 1 (sFlt-1)/Placental Growth Factor (PlGF) Ratio and Uterine Doppler Ultrasound in Women at Risk.

Hypertensive disorders of pregnancy (HDPs) represent a significant source of severe maternal and fetal morbidity. Screening strategies relying on traditional medical history and clinical risk factors have traditionally shown relatively modest performance, mainly in the prediction of preeclampsia, displaying a sensitivity of 37% for the early-onset form and 29% for the late-onset form. The development of more accurate predictive and diagnostic models of preeclampsia in the early stages of pregnancy represents a matter of high priority. The aim of the present paper is to create an effective second trimester prediction algorithm of early-onset HDP occurrence and severity, by combining the following two biochemical markers: a soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio and uterine artery Doppler ultrasound parameters, namely the pulsatility index (PI) and the resistivity index (RI), in a population of high-risk pregnant women, initially assessed through traditional risk factors. A prospective single-center observational longitudinal study was conducted, in which 100 women with singleton pregnancy and traditional clinical and medical history risk factors for preeclampsia were enrolled at 24 weeks of gestation. Shortly after study enrollment, all women had their sFlt-1 and PlGF levels and mean uterine artery PI and RI determined. All pregnancies were followed up until delivery. Receiver operating characteristic (ROC) analysis established algorithms based on cutoffs for the prediction of the later development of preeclampsia: PI 1.25 (96.15% sensitivity, 86.49% specificity), RI 0.62 (84.6% sensitivity, 89.2% specificity) and sFlt-1/PlGF ratio 59.55 (100% sensitivity, 89.2% specificity). The sFlt-1/PlGF ratio was the best predictor for preeclampsia, as it displayed the highest area under the curve (AUC) of 0.973. The prediction algorithm for the severe form of preeclampsia, complicated by fetal growth restriction leading to preterm birth, antepartum fetal demise or acute fetal distress with a cerebro-placental ratio of <one consisted of the following cutoffs: PI 1.44 (93.75% sensitivity, 95.24% specificity), RI 0.69 (87.5% sensitivity, 100% specificity) and sFlt-1/PlGF ratio 102.74 (93.75% sensitivity, 95.2% specificity). These algorithms may significantly enhance the prediction accuracy of preeclampsia compared to traditional risk factors. The combination of the sFlt-1/PlGF ratio with mean uterine PI and RI in particular displayed an improved performance in the prediction of severe preeclampsia with the above-mentioned complications, compared to the biochemical markers or uterine Doppler parameters used alone. Therefore, HDP screening strategies should increasingly focus on implementing such algorithms for women who are initially regarded as high risk based on traditional risk factors, in order to properly diagnose HDP and properly limit or manage the later maternal and fetal complications.

Prediction of severe preeclampsia in machine learning

This study aimed to find out the blood data characteristics of patients and explore the correlation between severe preeclampsia and blood index value. Provide assistance for the early attention direction of severe preeclampsia diagnosis and treatment. 19,653 pregnant women presenting to the West China Second University Hospital, Sichuan University from January 2017 to April 2019. After screening, a total of 248 patients, 124 severe preeclampsia cases, and 124 controls were selected for this study. Forty-three blood examination variables were obtained from routine blood work, hepatic, renal and coagulation function examination. Light gradient boosting machine (light GBM), decision tree and random forest were used for date diving. We randomly divided 35% of the original data as a testing set to conduct internal validation of the performance of the prediction model. The area under receiver operating characteristic curve (AUC) was used as the main score to compare the three methods. Finally, a binary classification light GBM model based on aspartate aminotransferase, direct bilirubin and activated partial thromboplastin time ratio can predict severe preeclampsia with sensitivity of 88.37%, specificity of 77.27%, AUC of 89.74% and positive predictive value of 65.96%. We believe relevant quantifiable indicators can establish an effective prediction model, which can provide guidance for early detection and prevention of severe preeclampsia.

Prediction of severe pre-eclampsia in low-risk women

Aim. To find the predictors of severe pre-eclampsia in women without any established risk factors.Materials and Methods. We consecutively recruited 200 pregnant women (100 with severe pre-eclampsia and 100 with uncomplicated pregnancy and successful delivery). Criteria of inclusion were age from 18 to 35 years, absence of significant comorbid conditions (cardiovascular diseases, autoimmune diseases, metabolic disorders, and kidney diseases), absence of family history and past medical history of pre-eclampsia and thromboembolism, singleton pregnancy, and body mass index in the first trimester &lt; 35 kg/m2 . We assessed allele and genotype distribution across several gene polymorphisms (ADD1-1378G&gt;T, AGT704T&gt;C, AGT-521C&gt;T, AGTR1-1166A&gt;C, AGTR2-1675G&gt;A, NO3-894G&gt;C, and NO3-786T&gt;C) potentially associated with severe pre-eclampsia.Results. We found that the combination of AGTR2-1675АA and eNOS3-786СC polymorphisms (p = 0.04), bacteriuria (p &lt; 0.001), acute respiratory infections (p = 0.011) and acute vulvovaginitis in second and third trimesters (p = 0.013), smoking (p &lt; 0.001), and past medical history of abortions (p = 0.017) were risk factors of severe pre-eclampsia.Conclusions. Predictors of severe pre-eclampsia revealed in this study can be used in the development of personalised prognostication during pregnancy in patients without conventional risk factors of pre-eclampsia.

Validation of ultrasound criteria for prediction of severe preeclampsia in a Peruvian population

espanolObjetivo: validar criterios de flujometria para predecir preeclampsia severa a partir de la elaboracion de rangos referenciales propios del indice de pulsatilidad de la arteria uterina en funcion de la edad gestacional y su asociacion a la edad materna, en una amplia muestra de la poblacion peruana. Material y metodos: estudio retrospectivo en 8.392 gestantes atendidas en un centro de referencia nacional materno perinatal nivel III en Peru, entre el 2009 y 2016. La muestra fue seleccionada aleatoriamente y dividida en: muestra de elaboracion para la construccion de curvas referenciales del indice de pulsatilidad promedio de las arterias uterinas segun la edad gestacional y asociacion con la edad materna de riesgo; y una segunda muestra para validacion de los criterios. Se uso analisis multivariado, medicion de la capacidad diagnostica y predictiva de los criterios. Resultados: el area bajo la curva ROC para el indice de pulsatilidad promedio de las arterias uterinas fue 0,61 (IC95%=0,58-0,64), para valores mayores a su percentil 95 0,66 (IC95%=0,63-0,68), para la edad materna de riesgo 0,60 (IC95%=0,57-0,63). La asociacion de un valor mayor al percentil 95 y edad materna de riesgo presento un area significativa mayor 0,72 (IC95%=0,688-0,742). Conclusiones: el indice de pulsatilidad promedio de las arterias uterinas ayuda a predecir la preeclampsia severa; sin embargo la aplicacion de valores por encima del percentil 95 y asociado a la edad materna de riesgo mejora la identificacion de preeclampsia severa con un 99% de especificidad y un valor predictivo positivo del 89% en nuestra poblacion EnglishObjective: To validate ultrasound criteria for prediction of severe preeclampsia based on the generation of appropriate reference values of the uterine artery pulsatility index according to gestational age and maternal age in a large sample of Peruvian women. Material and methods: We performed a retrospective study of 8,392 pregnant women attended in a level III maternal perinatal referral center in Peru between 2009 and 2016. The sample was randomly selected and divided into 2 groups: the study sample, in which reference curves of the mean uterine artery pulsatility index were constructed according to gestational age and at-risk maternal age (≤15 years and >35 years); and the validation sample, in which the criteria were validated. Multivariate analysis was applied, and the diagnostic and predictive value of the criteria were measured. Results: The area under the ROC curve was 0.61 (95%CI, 0.58-0.64) for the mean uterine artery pulsatility index, 0.66 (95%CI, 0.63-0.68) for values higher than its 95th percentile, and 0.60 (95%CI, 0.57-0.63) for at-risk maternal age. The combination of a value greater than the 95th percentile and at-risk maternal age generated a greater significant area (0.72 [95%CI, 0.688-0.742]) than the others separately. Conclusions: The mean uterine artery pulsatility index helps us to predict severe preeclampsia. However, the application of values above the 95th percentile combined with at-risk maternal age improved the identification of severe preeclampsia in our population, with a specificity of 99% and a positive predictive value of 89%.

Optical Coherence Tomography Findings in Pre-Eclampsia: A Preliminary Receiver Operating Characteristic Analysis on Choroidal Thickness for Disease Severity

ABSTRACTPurpose: To evaluate qualitative optical coherence tomography (OCT) findings and quantitative parameters, such as central macular thickness (CMT) and subfoveolar choroidal thickness (SFCT), in the eyes of preeclamptic women.Methods: The prospective, comparative, cross-sectional study included 52 eyes of 52 preeclamptic (PE) women and 54 eyes of 54 healthy pregnant women in their second or third trimester. Central macular thickness (CMT), subfoveolar choroidal thickness (SFCT), were evaluated in relation to presence of positive qualitative OCT findings such as any subretinal or intraretinal fluid, irregularity on the external photoreceptor and RPE layer, or presence of pigment epithelial detachment.Results: No significant difference was detected between the PE group and the healthy pregnant group with respect to CMT (P= 0.905), but the mean SFCT value was significantly higher in the PE group than in the healthy pregnant group (391.4 ± 71.1 vs 331.5 ± 53.8 µm, P < 0.001). Receiver operating characteristic analysis revealed that SFCT could predict qualitative OCT findings in preeclampsia, and the optimal cut-off value was 400 µm with a sensitivity of 91% and a specificity of 85%.Conclusion: The eyes of preeclamptic women, and particularly those with positive qualitative OCT findings, showed significantly increased SFCT values. A preliminary cut-off level of 400 µm for SFCT is proposed for the prediction of severe preeclampsia.

O21. First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with later pre-eclampsia

Introduction First trimester serum placental growth factor (PlGF) predicts early-onset pre-eclampsia (diagnosis Objectives To study the accuracy of using combined maternal serum %hCG-h, PlGF, PAPP-A and maternal risk factors in prediction of pre-eclampsia. Methods We determined gestational-age-adjusted concentrations of PlGF, PAPP-A, hCG (Perkin Elmer Wallac Oy, Turku, Finland) and hCG-h (in-house immunofluorometric assay) in maternal serum at 8–13 weeks of gestation. The study consisted of 98 women who later developed pre-eclampsia and 177 pregnant controls. Of the cases, 24 developed preterm pre-eclampsia (diagnosis 160/110mmHg, proteinuria>5g/24h and/or hemolysis, elevated liver enzymes and low platelet count –syndrome). Results Serum PlGF, %hCG-h and PAPP-A were lower in women with later preterm or severe pre-eclampsia than in controls. In receiver-operating characteristics (ROC) curve analysis the area under the curve (AUC) was 0.680 for PlGF, 0.699 for %hCG-h and 0.714 for PAPP-A to predict preterm pre-eclampsia. AUC values for prediction of severe pre-eclampsia were 0.677, 0.702 and 0.677, respectively. When PlGF, %hCG-h and PAPP-A were combined by logistic regression analysis the AUC value was 0.830 for preterm pre-eclampsia and 0.824 for severe pre-eclampsia. Combination of PlGF, %hCG-h, PAPP-A and maternal risk factors including nulliparity and first-trimester mean arterial pressure (MAP) gave an AUC value of 0.805 for preterm pre-eclampsia and 0.882 for severe pre-eclampsia. When PlGF was removed from the analysis the AUC value was 0.803 for preterm pre-eclampsia and 0.878 for severe pre-eclampsia. When %hCG-h was removed the AUC values were 0.756 and 0.840, respectively. Conclusions Combining %hCG-h with PlGF, PAPP-A and maternal risk factors in first trimester improves prediction of later preterm or severe pre-eclampsia. %hCG-h tended to give better AUC values than PlGF when combined with PAPP-A and maternal risk factors. Thus, in first trimester %hCG-h might be superior to PlGF for prediction of preterm or severe pre-eclampsia and it should be further investigated in risk models of pre-eclampsia.

590: Successfully overcoming barriers to genetic counseling through national telephone genetic counseling service

589 First-trimester prediction of preeclampsia using soluble P-selectin,follistatin-related protein 3, complement 3a, soluble TNF receptor type 1, PAPP-A, AFP, inhibin A, placental growth factor, uterine artery Doppler and maternal characteristics Lorraine Dugoff, Howard Cuckle, Nicholas Behrendt, Darleen Cioffi-Ragan, Leslie Myers, John Hobbins University of Pennsylvania, Obstetrics and Gynecology, Philadelphia, PA, Columbia University Medical Center, Obstetrics and Gynecology, New York, NY, University of Colorado, Obstetrics and Gynecology, Aurora, CO OBJECTIVE: To estimate the efficiency of first-trimester serum markers and uterine artery Doppler (UtA) in the prediction of severe preeclampsia (SPE). STUDY DESIGN: This is a prospective cohort study of patients presenting for aneuploidy screening between 11-14 weeks’ gestation. Maternal serum levels of soluble P-selectin, follistatin-related protein 3, complement 3a, soluble TNF receptor type 1, PAPP-A, AFP, inhibin A(inhA) and placental growth factor(PlGF) were measured by immunoassay and mean UtA resistance indices(RI) were calculated. The primary outcome was SPE. A secondary outcome of all PE including mild preeclampsia was also evaluated. Marker levels were expressed in multiples of the normal median (MOM), adjusting for gestation, weight, smoking and ethnicity. Logistic regression analysis was used to model performance. Maternal characteristics identified as significant in a univariate analysis were included in the models. Predicted sensitivity, specificity, and area under the receiver-operating characteristic curves were used to compare the screening efficiency of the models. RESULTS: Of 1028 patients, 26(2.5%) had SPE and 56(5.4%) had PE. Median PlGF levels were lower in patients with SPE (0.83 MoM vs 0.98 MoM, P 0.05) and PE(0.90 MoM vs 0.98 MoM, P 0.05) compared to those without PE. AFP was significantly higher (1.15 MoM vs 1.00 MoM, P 0.05; 1.20 MoM vs 0.99 MoM, P 0.01). Median RI was significantly increased in PE (1.05 MoM vs 1.00 MoM, P 0.05) but not in SPE; similarly for inhA (1.09 MoM vs 0.99 MoM, P 0.05). For a fixed false positive rate of 20%, PlGF and AFP identified 49% of patients with SPE; combining these with prior risk factors did not improve the model efficiency. The detection rate for PE was 44% modeling with PlGF, AFP, inhA and RI. CONCLUSION: First-trimester PlGF and AFP are each modestly predictive of SPE, but combining both improves detection.

Prediction of preeclampsia: liver function tests during the first 20 gestational weeks

Objective: To examine whether plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the first 20 weeks of pregnancy can predict preeclampsia in the second half of pregnancy. Methods: The study population included 150,10 registered births. Receiver operating characteristic (ROC) curve analysis was used to describe the relationship between different values of AST and ALT during the first 20 weeks of pregnancy in the prediction of preeclampsia. Results: Using ROC curve analyses, elevated ALT levels were significantly associated with both mild preeclampsia (p < 0.001) and severe preeclampsia (p = 0.032). However, an ALT level of 50 IU/L had a sensitivity of only 3.3% (despite a specificity of 97%) in the prediction of severe preeclampsia. While no significant association was noted between AST levels and mild preeclampsia (p = 0.669), elevated levels of AST during this period were significantly associated with severe preeclampsia (p = 0.027). However, AST of 50I U/L had a sensitivity of only 2.0% (despite a specificity of 98%) in the prediction of severe preeclampsia. Conclusions: Higher levels of the liver enzymes AST and ALT during the first 20 weeks of pregnancy are associated with higher risk for the development of severe preeclampsia in the second half of the pregnancy. Nevertheless, there is no clinical cutoff value that can be practically used for the prediction of preeclampsia.

P179 Prediction of severe preeclampsia with maternal history, serum screening and uterine artery Doppler velocimetry

P179 Prediction of severe preeclampsia with maternal history, serum screening and uterine artery Doppler velocimetry

Doppler-Sonographiescreening der A. uterina in der gynäkologischen Praxis

Zu prüfen war die Frage, ob ein in die übliche Schwangerschaftsvorsorge integriertes Doppler-Sonographiescreening der A. uterina Hochrisikoschwangere für Erkrankungen aus dem Formenkreis der Präeklampsie und Wachstumsretardierung zuverlässig zu detektieren vermag.

Magnesium in disease: a review with special emphasis on the serum ionized magnesium.

This review deals with the six main clinical situations related to magnesium or one of its fractions, including ionized magnesium: renal disease, hypertension, pre-eclampsia, diabetes mellitus, cardiac disease, and the administration of therapeutic drugs. Issues addressed are the physiological role of magnesium, eventual changes in its levels, and how these best can be monitored. In renal disease mostly moderate hypermagnesemia is seen; measuring ionized magnesium offers minimal advantage. In hypertension magnesium might be lowered but its measurement does not seem relevant. In the prediction of severe pre-eclampsia, elevated ionized magnesium concentration may play a role, but no unequivocal picture emerges. Low magnesium in blood may be cause for, or consequence of, diabetes mellitus. No special fraction clearly indicates magnesium deficiency leading to insulin resistance. Cardiac diseases are related to diminished magnesium levels. During myocardial infarction, serum magnesium drops. Total magnesium concentration in cardiac cells can be predicted from levels in sublingual or skeletal muscle cells. Most therapeutic drugs (diuretics, chemotherapeutics, immunosuppressive agents, antibiotics) cause hypomagnesemia due to increased urinary loss. It is concluded that most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease. Keeping in mind that only 1% of the total body magnesium pool is extracellular, no simple measurement of the real intracellular situation has emerged; measuring ionized magnesium in serum has little added value at present.

Prediction of pre-eclampsia with maternal mid-trimester total renin, inhibin A, AFP and free beta-hCG levels.

We wanted to study if maternal serum mid-trimester total renin, inhibin A, AFP or free beta-hCG levels predict the development of pre-eclampsia. Maternal serum alpha-fetoprotein (AFP) and human chorion gonadotrophin (beta-hCG) were evaluated in the screening programme for Down syndrome in 4356 patients prospectively. Data on pregnancy outcome were available in 1242 women. Pregnancy-induced hypertension (PIH) developed in 69 women, 282 women with uneventful pregnancy outcome were selected for controls. Serum total renin and inhibin A levels were measured retrospectively in the trisomy screening samples of 69 and 30 patients who later developed PIH, and in 282 and 7 patients, respectively, who had an uneventful pregnancy outcome. No significant differences were found in the levels of maternal mid-trimester serum total renin, inhibin A or free beta-hCG levels between PIH and healthy women. The multiples of the median (MoM) of AFP values were significantly higher in the subgroup of patients who later developed severe pre-eclampsia than in patients with mild pre-eclampsia or gestational hypertension and healthy pregnant women. Maternal mid-trimester serum levels of total renin, inhibin A and free beta-hCG are not predictive for development of PIH. High mid-trimester serum AFP values may help in the prediction of severe pre-eclampsia.