Exploring Preeclampsia: A Comprehensive Overview

The ratio between sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (Placental Growth Factor) was recently introduced to aid in the management of hypertensive disorders of pregnancy and fetal growth restriction, but it has limitations. This study proposes a new angiogenic classification of PlGF and sFlt-1 to enhance maternal and fetal risk assessment in pregnancies with suspected placental dysfunction. A retrospective analysis was conducted on hospitalized singleton pregnancies beyond the 20th week complicated by hypertensive disorders of pregnancy and/or fetal growth restriction. Patients were classified based on sFlt-1/PlGF (low, medium, high, very high) and into the nine possible combinations using PlGF and sFlt-1 gestational age-specific levels: (1) PlGF and sFlt-1 within range; (2) PlGF in range, sFlt-1<range; (3) PlGF in range, sFlt-1>range; (4) PlGF<range, sFlt-1 in range; (5) PlGF and sFlt-1<range; (6) PlGF<range, sFlt-1>range; (7) PlGF>range, sFlt-1 in range; (8) PlGF>range, sFlt-1<range; (9) PlGF and sFlt-1>range. The cohort included 227 patients. The most common categories were 1, 3, 4, and 6. Categories 4 and 6 had a higher proportion of fetal growth restriction, whereas categories 3 and 6, presented a greater risk of severe maternal complications. Category 6 exhibited the highest risk of adverse maternal-fetal outcomes; conversely, category 1 was the category at the lowest risk for complications. Notably, 40% of patients classified as low or medium risk by the sFlt-1/PlGF were high-risk by our classification. Evaluation of actual PlGF and sFlt-1 levels rather than set cut-off ratios can improve the risk stratification of clinical manifestations of placental pathology.

POS0542 DISEASE ACTIVITY IN PREGNANT WOMEN WITH RHEUMATOID ARTHRITIS: IMPACT ON THE SOLUBLE FMS-LIKE TYROSINE KINASE-1 TO PLACENTAL GROWTH FACTOR RATIO

Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study

sFlt-1 (serum soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) can be used to predict the development of severe preeclampsia. The association between sFlt-1/PlGF during pregnancy and long-term risk of hypertension is unclear. This is a retrospective cohort study of patients enrolled from 2006 to 2008 in the ongoing LIFECODES biobank. Mean sFlt-1 and PlGF levels were collected in the second half of pregnancy. Electronic medical record review identified those who developed hypertension over 15 year follow-up. Adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% CI for the time to diagnosis of hypertension. Of the n=993 participants, n=260 (29.18%) were diagnosed with stage 1 and n=169 (17.0%) were diagnosed with stage 2 hypertension. One hundred thirteen of the participants in the database had a diagnosis of gestational hypertension or preeclampsia. A history of preeclampsia or a history of gestational hypertension was both significantly associated with developing hypertension later in life, with adjusted hazard ratios of 2.17 (95% CI, 1.44-3.28) and 3.50 (95% CI, 2.21-5.54), respectively. We observed no significant association between the hazard of developing hypertension and sFlt-1/PlGF. However, mean PlGF levels in those who remained normotensive in the follow-up were significantly higher, 546.7 pg/mL (SD=369.5), compared with those who developed hypertension, 513.7 pg/mL (SD=389.9; P=0.008). A history of hypertensive disease of pregnancy was significantly associated with the hazard of developing HTN later in life, while elevated sFlt-1/PlGF levels were not. PlGF levels alone were significantly lower in those who developed hypertension later.

Angiogenic markers in pregnancies conceived through in vitro fertilization

COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38–85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

Introduction: Pre-eclampsia (PE), a pregnancy induced hypertensive disorder affects approximately 8-10% of all pregnancies in developing countries. A highly sensitive and specific marker for diagnosis of PE is the need of the hour as diagnostic criteria are still based on non-specific clinical symptoms, ultrasound, and laboratory findings. Imbalance in the placental release of various angiogenesis regulatory factors to the maternal circulation is one of the significant contributors to its clinical manifestations. Low levels of pro-angiogenic biomarker Placental Growth Factor (PLGF) are detectable several weeks before clinical presentation of PE. Aim: To determine the association of serum levels of PLGF with PE in second and third trimester of pregnancy. Materials and Methods: A prospective cohort study was performed in a tertiary care hospital from December 2018 to November 2021, on 130 patients by dividing study participants into two groups: Pre-eclamptic cases, Normotensive controls. At enrollment in second trimester (24-28 weeks) and during third trimester (beyond 28 weeks) serum PLGF concentration was measured by using the Enzyme-linked Immunosorbent Assay (ELISA) kit method. Data was statistically analysed. Student’s t-test was used for comparing differences between study groups. The chi-square test was used to compare qualitative categorical data. Evaluation of the Area Under the Curve (AUC), diagnostic accuracy, sensitivity and specificity was done by Receiver Operating Characteristics (ROC) curve analysis done using software defined cut-off values. Results: Total of 115 patients were analysed in the present study with 55 patients in group 1(mean age: 25.83±3.27 years) and 60 patients in group 2 (mean age: 30.52±5.63 years) When compared with normotensive group PLGF levels were significantly lower in pre-eclamptic group with median 16.27 ng/mL versus 12.20 ng/ mL (p &lt;0.001) in second and 14.05 ng/mL versus 10.50 ng/mL (p &lt;0.001) in third trimesters respectively. ROC curve analysis using cut-off point of 14.91 ng/mL showed sensitivity 80%, specificity 96.7%, AUC 0.896, 95%CI:(0.832-.959) in second trimester and in third trimester at cut-off point of 13 ng/mL sensitivity 73%, specificity 96.7%, AUC 0.882 95% CI:(0.816-.948) was found. Conclusion: PLGF may be used as a biomarker for early prediction, diagnosis, and management of PE. It might serve as ideal discriminating biochemical markers of PE. In the near future, the clinical utility of disease specific angiogenic biomarker in early detection of PE might improve health outcomes by preventing adverse maternal and neonatal outcomes and serious complications.

Antenatal care has been crucial in reducing maternal mortality. Currently, screening programs of pregnant women include blood pressure (BP) measurements, urine protein tests, and the identification of risk factors. Home monitoring can enhance the early detection and management of pregnancy-related hypertension, while also empowering women to take an active role in their own health care. This study aimed to evaluate the reliability and accuracy of contactless BP monitoring using the Anura smartphone app and to compare it to conventional manual cuff measurements. This was done in normotensive and high-risk pregnancies, as well as in women diagnosed with preeclampsia. A secondary objective was to assess women's experience using the Anura app. Pregnant women with normotensive or high-risk pregnancies were enrolled from pregnancy weeks 8-14, and women with preeclampsia were enrolled at the time of diagnosis. The 3 study groups consisted of 132 women with normotensive pregnancies, 40 women with high-risk pregnancies, and 87 women with preeclampsia. They were instructed to use the Anura smartphone app and perform a 30-second facial scan, alongside manual BP measurements, throughout pregnancy. Differences between the 2 methods were analyzed with linear mixed models accounting for repeated measures, reporting beta coefficients with 95% CIs, stratified by patient group and trimester. Outliers were detected visually in the Bland-Altman plots. A digital survey was answered in the Anura app at gestational weeks 37-39, about their experiences using the Anura app. A total of 4932 BP measurements were recorded with Anura, of which 539 had corresponding manual measurements. In normotensive pregnancies, Anura consistently showed slightly higher diastolic values (approximately 5-7 mm Hg) and lower systolic values, with significant differences in the second and third trimesters. In high-risk pregnancies, both the systolic and diastolic BP were generally lower with Anura, especially in the second and third trimesters, while women with preeclampsia showed the largest differences, with Anura clearly showing lower systolic and diastolic values. Bland-Altman analyses confirmed these patterns and showed increasing variability and wider limits of agreement in the high-risk pregnancies with preeclampsia. Of 172 women with normotensive and high-risk pregnancies, 56 (32.5%) evaluated their experiences that were predominantly positive, with high perceived safety, better control, and a feeling of increased responsibility for their own health. Some experienced the measurement as somewhat uncomfortable. The Anura app is well accepted by pregnant women and supported them to take an active role in their own health care. Agreement with manual BP measurements was acceptable in normotensive pregnancies but lower in high-risk and preeclamptic pregnancies. These findings indicate potential for Anura as a complementary self-monitoring tool. Further development is needed to improve the app's accuracy in high-risk groups before broader implementation can be recommended.

Hypertension Editors' Picks: Preeclampsia, Pregnancy, and Hypertension.

BackgroundPregnancy induced hypertension (PIH) is characterized by aberrant uterine arterial remodeling, a process tightly associated with an imbalance between placental growth factor (PlGF) and soluble fms like tyrosine kinase 1 (sFlt 1) as well as the down regulation of matrix metalloproteinases 2/9 (MMP 2/9). This study investigated the regulatory effect of PlGF on the two pore domain potassium channel KCNK2 and its downstream targets MMP 2/9, and explored the role of the PlGF KCNK2 MMP 2/9 axis in PIH related uterine arterial dysfunction.MethodsIn vitro, human aortic endothelial cells (HAECs) were assessed for proliferation and migration using CCK 8 and Transwell assays. Nitric oxide (NO) and endothelin 1 (ET 1) levels were quantified by ELISA, while KCNK2 and MMP 2/9 expression was analyzed by Western blotting. In vivo, a Sprague Dawley rat PIH model was established to monitor blood pressure and 24 h urinary protein. Hematoxylin–eosin staining was used to measure uterine arterial intimal thickness; endothelial nitric oxide synthase (eNOS) and ET 1 localization was determined by immunohistochemistry, and KCNK2 as well as MMP 2/9 expression was quantified by immunohistochemistry and Western blotting.Results2,2,2 Trichloroethanol and PlGF significantly enhanced endothelial cell proliferation and migration, increased NO, decreased ET 1, and up regulated KCNK2 and MMP 2/9 expression (P < 0.05); ropivacaine produced opposite effects. PIH rats exhibited markedly elevated blood pressure and urinary protein, intimal thickening, reduced eNOS and elevated ET 1, together with diminished MMP 2/9 expression. Combined treatment with PlGF and 2,2,2 trichloroethanol lowered blood pressure and urinary protein, attenuated intimal thickness, increased eNOS and decreased ET 1, and up regulated KCNK2 and MMP 2/9 (P < 0.05).Conclusion2,2,2 Trichloroethanol activates KCNK2, elevates MMP 2/9, and improves uterine arterial endothelial function, while PlGF synergizes with KCNK2 signaling to potentiate these effects. The PlGF KCNK2 MMP 2/9 axis plays a pivotal regulatory role in the vascular pathology of PIH, highlighting its potential as a therapeutic target for PIH related vascular dysfunction.

Maternal and foetal health is significantly influenced by nutrition, because it is widely acknowledged that a healthy diet in pregnancy is the basis for long-standing health. The objectives of our study were to determine the frequencies of iron, calcium, magnesium deficiencies, malnutrition among young pregnant women and their effects on feto-maternal outcome. The effects of nutritional counselling / education in improving maternal nutrition and comparison between fetal maternal health outcomes at tertiary care hospital were measured. Methodology: Total 191 participants were selected study purpose, 91subjects were labelled study group and 100 were labelled comparison group. Study subjects were provided nutritional / diet plan according to the nutritional status and deficiencies and followed for three months. Pregnancy outcomes were measured and compared with comparison group. Sociodemographic information, anthropometric measure, laboratory investigations and dietary plans were collected and analyzed on SPSS (version 26.0), various tests of significance were applied for association and correlation. Results: All women were primigravida having age from 18 to 26 years, belonging to both urban and rural areas and majority of participants were from middle class families. Mean gestational age of the study group in their 1st visit was 26.02 ± 1.92 and in 2nd visit it was 36.62 ± 1.29 while in comparison group mean gestational age at the time of delivery was 36.15 ± 2.04. Mean weight was 69.12 ± 4.56 for study group and mean weight was 65.51 ± 4.87 for comparison group at the time of delivery (p-value 0.535). Mean gestational weight gain measured was 12.21 ± 1.85 for study group at the time of delivery and mean gestational weight gain was 9.71 ± 1.69 for comparison group at the time of delivery (p-value 0.012). Mean hemoglobin level of study group was 10.74 ± 1.32 mg/dl at their 1st visit and 12.05 ± 1.39 mg/dl at their 2nd visit while in comparison group mean hemoglobin level was 10.07 ± 2.06 mg/dl. Statistical significant values were (p-value 0.024) at 95% confidence level. The study group's mean serum calcium level was 8.86 ± 1.04 mg/dl at the first visit and 9.85 ± 0.72 at the second. The mean serum calcium level for the comparison group was 8.75 ± 1.11. At a 95% confidence level, the statistically significant values were (p-value 0.000). The study group's mean serum Magnesium level was 1.81 ± 0.30 mg/dl at their first visit and 2.15 ± 0.12 mg/dl at their second visit, whereas the comparison group's mean was 1.95 ± 0.35 mg/dl. At a 95% confidence level, statistically significant values were (p-value 0.000). Proper nutritional counselling and diet plan throughout pregnancy is strongly associated with significantly reduced mortality and morbidity in both mother and neonate. Good and balanced nutrition significantly improved feto-maternal health outcomes. All the parameters under study were improved after intervention. There was a statistically significant correlation between maternal nutrition and health outcomes (p-value 0.003, OR- 1.2), while in comparison group there was increased risk of poor health outcome (p-value 0.749, OR 2.63) from our study data. Correlation between maternal nutritional status and health outcome of the newborn and there was highly statistically significant association b/w maternal nutrition and health outcome of the babies (p-value 0.012, OR- 2.458), while in comparison group there was increased risk of poor health outcome of babies was (p-value 0.749, 0R 6.934). Knowledge of study group was assessed before intervention. It was noted that there was gap between knowledge and nutritional status of the participants. P-value 0.035 was significant at in comparison group.

Imbalance between angiogenesis-related factors is closely related to the development of preeclampsia. The objective was to estimate the most effective and accurate predictive biomarker among levels and ratios of angiogenesis-related factors, including soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin, placental growth factor (PlGF), and transforming growth factor-beta1 (TGF-beta1), in women who subsequently developed preeclampsia. A nested cohort study was conducted to estimate the levels of sFlt-1, soluble endoglin, PlGF, and TGF-beta1 in plasma collected in the second trimester from 40 women who subsequently developed preeclampsia and 100 contemporaneous normotensive women. Levels of sFlt-1 and soluble endoglin were significantly higher in women with preeclampsia than in normotensive women, whereas levels of PlGF and TGF-beta1 were lower (P<.001). In women with preeclampsia, sFlt-1/PlGF, soluble endoglin/TGF-beta1, and the combined ratio of (sFlt-1+soluble endoglin)/(PlGF+TGF-beta1) were significantly higher than in normotensive women (P<.001) and even greater in severe preeclampsia with preterm delivery compared with mild preeclampsia with term delivery (P<.05). At equivalent sensitivity (85%), the false-positive rate was 45% for sFlt-1, 41% for soluble endoglin, 33% for sFlt-1/PlGF, 21% for soluble endoglin/TGF-beta1, and 10% for the combined ratio. After adjusting for potential confounding factors, the risks for developing preeclampsia were as follows: odds ratio (OR) 6.9 [95% confidence interval 2.3-20.7] for sFlt-1 level, 7.1 [2.3-21.7] for soluble endoglin level, 6.8 [2.4-19.4] for sFlt-1/PlGF, 38.8 [9.8-154.3] for soluble endoglin/TGF-beta1, and 74.8 [17.6-316.7] for the combined ratio. The combined ratio of angiogenesis-related factors showed the lowest false-positive rate and the highest OR for prediction of preeclampsia, indicating that it may provide more effective prediction of development of preeclampsia. II.

Preeclampsia is one of the most common as well as most severe complications of pregnancy, characterized by new-onset hypertension and proteinuria or other organ dysfunction. It predominantly occurs after 20 weeks of gestation. Very rarely, it can be triggered earlier in some specific situations. Here we report a case of fetal triploidy presenting as an extraordinarily early-onset preeclampsia. A healthy 36-year-old multiparous woman who had conceived naturally was hospitalized due to acute-onset severe hypertension accompanied by proteinuria at 18 weeks of gestation. Laboratory testing ruled out the presence of underlying maternal disease. Ultrasound findings, including multicystic large placenta and multiple fetal anomalies, strongly suggested fetal triploidy. Maternal ovaries showed hyperreactio luteinalis. The soluble fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) ratio was elevated, at 270. Medical abortion was carried out at 19 weeks of gestation; thereafter, her symptoms quickly resolved. Fetal triploidy was confirmed by genetic testing. We should be aware that fetal disorders including triploidy as well as pre-existing maternal diseases can provoke such very early-onset preeclampsia. Fetal ultrasound evaluation is critical and the sFlt-1/PlGF ratio is important for prompt diagnosis and management to prevent adverse maternal outcomes associated with atypical preeclampsia before 20 weeks of gestation.

Preeclampsia (PE) is a potentially life-threatening multisystem disorder affecting maternal and fetal health and is associated with impaired angiogenesis, endothelial dysfunction, inflammation, and apoptosis. In this study, we characterized molecular, histopathological, and clinical alterations in placentas from 30 women with PE compared with 30 normotensive controls. Placental tissues underwent macroscopic evaluation, histopathology, immunohistochemistry for α-Klotho, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and tumor necrosis factor-α (TNF-α), alongside TUNEL assay for apoptosis. PE pregnancies were associated with earlier delivery, lower neonatal birth weight, reduced placental weight and volume, and decreased maternal total protein and albumin levels. Histologically, PE placentas exhibited increased syncytial knots, intervillous fibrin deposition, distal villous hypoplasia, chorangiosis, avascular villi, and calcifications. Immunohistochemical analyses indicated reduced expression of α-Klotho, eNOS, VEGF, and PlGF, with increased TNF-α expression and higher apoptotic index. α-Klotho expression correlated positively with angiogenic markers, placental weight, and birth weight, and negatively with TNF-α and apoptosis. Multivariate regression analyses suggested that PE is associated with increased placental apoptosis and TNF-α expression, as well as reduced α-Klotho, eNOS, VEGF, and PlGF expression, and with lower birth weight, primarily mediated by prematurity. Early-onset PE exhibited more pronounced α-Klotho reduction with relatively preserved eNOS expression, suggesting potential compensatory endothelial responses, while magnesium sulfate or antihypertensive therapy did not significantly influence molecular profiles. These findings suggest that PE is linked to coordinated alterations in angiogenic, endothelial, and inflammatory pathways associated with placental structural changes and adverse perinatal outcomes. Observed alterations in α-Klotho and angiogenic markers highlight potential pathways for further investigation into targeted molecular interventions. This study is limited by its single-center, and relatively small sample size, which may limit generalizability, and causal relationships cannot be established; further multi-center prospective studies are warranted.

Electronic fetal monitoring (EFM) is used for the majority of births that occur in the United States. While there are indications for use of EFM for women with high-risk pregnancies, its use in low-risk pregnancies is less evidence-based. In low-risk women, the use of EFM is associated with an increased risk for cesarean birth compared with the use of intermittent auscultation of the fetal heart rate. The purpose of this investigation was to evaluate the existence of evidence-based information on fetal heart rate monitoring in popular consumer-focused maternity books and Web sites. Content analysis of information in consumer-oriented Web sites and books was completed using the NVivo software (QRSinternational, Melbourne, Australia). Themes identified included lack of clear terminology when discussing fetal monitoring, use of broad categories such as low risk and high risk, limited presentation of information about intermittent auscultation, and presentation of EFM as the standard of care, particularly upon admission into the labor unit. More than one-third of the sources did not mention auscultation, and conflicting information about monitoring methods was presented. The availability of accurate, publically accessible information offers consumers the opportunity to translate knowledge into the power to seek evidence-based care practices during their maternity care experience.