Hypertensive states of pregnancyEstados hipertensivos del embarazo / Estados hipertensivos del embarazo

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.(AU)

Los estados hipertensivos del embarazo (EHE) siguen siendo una de las principales causas de morbilidad y mortalidad materna y fetal relacionada con el embarazo en todo el mundo, incluyen la hipertensión crónica, la hipertensión gestacional y la preeclampsia. Las mujeres afectadas y los recién nacidos también tienen un mayor riesgo de sufrir enfermedades cardiovasculares en el futuro, independientemente de los riesgos tradicionales de la enfermedad cardiovascular. A pesar de estos riesgos, las recomendaciones para un diagnóstico y un tratamiento óptimo han cambiado poco en las últimas décadas, probablemente por el miedo a las repercusiones fetales de la disminución de la presión arterial y la posible toxicidad farmacológica. En ese documento revisamos los criterios diagnósticos y la clasificación de los EHE, así como aspectos importantes en cuanto a fisiopatología y la detección temprana que permita la identificación precoz de las mujeres en riesgo, con el objetivo de prevenir tanto las secuelas inmediatas como a largo plazo. También se revisa el tratamiento profiláctico con aspirina de forma precoz y se realiza una aproximación terapéutica que implica una estrecha vigilancia materna y fetal, y si es necesario, el uso de fármacos seguros en cada situación. Esta revisión pretende dar una visión actualizada para la prevención, diagnóstico y tratamiento de los EHE que sea de utilidad en nuestra práctica clínica habitual.(AU)

Phenylbutyric acid inhibits hypoxia-induced trophoblast apoptosis and autophagy in preeclampsia via the PERK/ATF-4/CHOP pathway.

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia. To verify the underlying mechanisms of 4-PBA on PE, CCT020312, an activator of PERK, was also used. The results showed that 4-PBA restored hypoxia-induced trophoblast viability, inhibited HIF-1α protein expression, inflammation, and PERK/ATF-4/CHOP pathway. Hoechst 33342 staining and flow cytometry results confirmed that 4-PBA decreased hypoxia-induced apoptosis in trophoblasts. The results of the JC-1 analysis and apoptosis initiation enzyme activity assay also demonstrated that 4-PBA inhibited apoptosis related to the mitochondrial pathway. Furthermore, by detecting autophagy in trophoblasts, an increased number of autophagic vesicles, damaged mitochondria, enhanced dansylcadaverine fluorescence, enhanced levels of autophagy proteins Beclin-1, LC3II, and decreased p62 were seen in hypoxia-stimulated cells. These changes were reversed by 4-PBA. Furthermore, it was observed that CCT020312 reversed the effects of 4-PBA on the viability, apoptosis, and autophagosome number of hypoxia-induced trophoblasts. In summary, 4-PBA reduces autophagy and apoptosis via the PERK/ATF-4/CHOP pathway and mitochondrial pathway, thereby restoring the viability of hypoxic trophoblasts. These findings provide a solid evidence base for the use of 4-PBA in PE treatment and guide a new direction for improving the outcomes of patients with PE.

Endothelial progenitor cells control remodeling of uterine spiral arteries for the establishment of utero-placental circulation.

Placental ischemia, resulting from inadequate remodeling of uterine spiral arteries, is a factor in the development of preeclampsia. However, the effect of endothelial progenitor cells that play a role in the vascular injury-repair program is largely unexplored during remodeling. Here, we observe that preeclampsia-afflicted uterine spiral arteries transition to a synthetic phenotype in vascular smooth muscle cells and characterize the regulatory axis in endothelial progenitor cells during remodeling in human decidua basalis. Excessive sEng, secreted by AMP-activated protein kinase (AMPK)-deficient endothelial progenitor cells through the inhibition of HO-1, damages residual endothelium and leads to the accumulation of extracellular matrix produced by vascular smooth muscle cells during remodeling, which is further confirmed by animal models. Collectively, our findings suggest that the impaired functionality of endothelial progenitor cells contributes to the narrowing of remodeled uterine spiral arteries, leading to reduced utero-placental perfusion. This mechanism holds promise in elucidating the pathogenesis of preeclampsia.

Targeting JUNB to modulate M2 macrophage polarization in preeclampsia.

Preeclampsia (PE) is a complex disorder affecting pregnant women, leading to significant maternal and fetal morbidity and mortality. Understanding the cellular dynamics and molecular mechanisms underlying PE is crucial for developing effective therapeutic strategies. This study utilized single-cell RNA sequencing (scRNA-seq) to delineate the cellular landscape of the placenta in PE, identifying 11 distinct cell subpopulations, with macrophages playing a pivotal role in mediating cell-cell communication. Specifically, the transcription factor JUNB was found to be a key gene in macrophages from PE samples, influencing the interaction between macrophages and both epithelial and endothelial cells. Functional experiments indicated that interference with JUNB expression promoted macrophage polarization towards an M2 phenotype, which facilitated trophoblast invasion, migration, and angiogenesis. Mechanistically, JUNB regulated the MIIP/PI3K/AKT pathway, as evidenced by gene expression analysis following JUNB knockdown. The study further demonstrated that targeting JUNB could activate the PI3K/AKT pathway by transcriptionally activating MIIP, thus promoting M2 polarization and potentially delaying the onset of PE. These findings present new insights into the pathogenesis of PE and suggest a novel therapeutic approach by modulating macrophage polarization.

Levels of serum ß-human chorionic gonadotropin after embryo transfer and subsequent miscarriage, pre-eclampsia, and intrauterine growth restriction.

Background: This study aimed to examine maternal serum concentration of ß-human chorionic gonadotropin (ß-hCG) on Day 16 after embryo transfer and risk of miscarriage, pre-eclampsia, and intrauterine growth restriction (IUGR). Methods: In this study, we evaluated 125 pregnancies following in vitro fertilization (IVF). ß-hCG concentrations were measured on the morning of Day 16 after embryo transfer. Baseline characteristics of the study participants were also recorded. Results: Concentrations of ß-hCG on Day 16 after embryo transfer were inversely associated with the higher risk of miscarriage (p < 0.001), but did not with pre-eclampsia and IUGR (p > 0.05). Spearman's correlation coefficient showed a reverse and significant association between ß-hCG and higher risk of miscarriage (σ = 0.531 and p < 0.001). There was a significant association between frozen embryo transfer and the risk of IUGR and pre-eclampsia (p = 0.005 and p = 0.023, respectively). Conclusions: Maternal serum concentrations of ß-hCG on Day 16 after IVF/embryo transfer were associated with the higher risk of miscarriage, but not pre-eclampsia and IUGR.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

Management of postpartum preeclampsia complicated by idiopathic pericarditis: A case report.

This case report discusses the rare occurrence of pericarditis with preeclampsia in the antepartum through to postpartum state. A woman in her 30s presented four days postnatally with positional central chest pain, elevated blood pressure and newly deranged liver function tests. Echocardiogram demonstrated new pleural effusion and she was diagnosed with preeclampsia and superimposed pericarditis. Her blood pressure was stabilised with a combination treatment regime of labetalol, enalapril and frusemide, whilst her pericarditis responded well to colchicine and ibuprofen. She was eventually discharge on enalapril and colchicine. By her 6-week follow-up she had made a full recovery and she had reported no recurrence of symptoms at the time of writing.

The Impact of Congestive Heart Failure on Outcomes in Patients Hospitalized With Preeclampsia.

INTRODUCTION: The purpose of this study was to determine the prevalence of congestive heart failure (CHF) among patients admitted with preeclampsia as well as to analyze the independent association of CHF with in-hospital outcomes among women with preeclampsia. METHODS: Data were obtained from the National (Nationwide) Inpatient Sample (NIS) from January 2016 to December 2019. We assessed the independent association of CHF with outcomes in patients admitted with preeclampsia. Predictors of mortality in patients admitted with preeclampsia were also analyzed. RESULTS: Women with preeclampsia in the United States between 2016 and 2019 were included in our analysis. A total of 256,010 cases were isolated, comprising 1150 patients with preeclampsia and CHF (0.45%). Multivariate analysis demonstrated that CHF in patients with preeclampsia was independently associated with several outcomes, among them cardiac arrest (adjusted OR (aOR) 4.635, p=0.004), ventricular tachycardia (aOR 17.487, p<0.001), pulmonary embolism (aOR 6.987, p<0.001), and eclampsia (aOR 2.503, p=0.011). Conversely, we found CHF to be protective against postpartum hemorrhage (aOR 0.665, p=0.003). Among the predictors of mortality in preeclampsia are age (aOR 1.062, p=0.022), Asian or Pacific Islander race (aOR 4.695, p=0.001), and CHF (aOR 25.457, p<0.001).  Conclusions: In a large cohort of patients admitted with preeclampsia, we found the prevalence of CHF to be 0.45%. CHF was associated with several adverse outcomes as well as increased length of stay.

Biomarker role of maternal soluble human leukocyte antigen G in pre-eclampsia: A meta-analysis.

INTRODUCTION: Human leukocyte antigen-G (HLA-G) is a non-classical class I HLA molecule shown to regulate the immunomodulation of maternal immune cells to prevent fetal tissue destruction. Low levels of freely circulating maternal soluble HLA-G (sHLA-G) have been observed in pre-eclampsia, however, no pooled evidence exists. This meta-analysis aimed to generate pooled findings on the association of sHLA-G levels with pre-eclampsia and is the first study to perform a trimester-wise comparison of the levels of sHLA-G in preeclamptic cases and normal pregnant controls. METHODS: The databases PubMed, Emba, Web of Science, and Google Scholar through May 31, 2023. Preeclamptic women were defined as cases and normal pregnancies as controls. Data on the level of sHLA-G in cases and controls was extracted and subjected to a meta-analysis using a random-effects model. The pooled effect was expressed in terms of standardized mean difference (SMD). Sensitivity analysis was performed to investigate the effect of the exclusion of each study on the pooled results. Publication bias was assessed statistically. RESULTS: Nine studies with altogether 567 PE cases and 1132 normal pregnancy controls were included in the meta-analysis. The first and third trimester levels of sHLA-G in PE cases were significantly lower than that of normal pregnant controls: (SMD: -0.84 [-1.29; -0.38]; p = .003; I2 = 54%) and (SMD: -0.39 [-0.71; -0.06]; p = .02; I2 = 79%) respectively. Sensitivity analysis revealed significant fluctuations in the pooled findings when few studies were excluded, raising questions on the consistency of results among studies. CONCLUSION: Although we found that first and third-trimester sHLA-G levels in pre-eclampsia are significantly lower, taking into consideration the inconsistent results from the sensitivity analysis, our findings advocate the demand for more studies with larger sample sizes to generate solid ground pooled evidence on the predictive role of sHLA-G in pre-eclampsia.

Pre-pregnancy body mass index and caesarean section in Andean women in Peru: a prospective cohort study.

BACKGROUND: During the last two decades, Caesarean section rates (C-sections), overweight and obesity rates increased in rural Peru. We examined the association between pre-pregnancy body mass index (BMI) and C-section in the province of San Marcos, Northern Andes-Peru. METHODS: This is a prospective cohort study. Participants were women receiving antenatal care in public health establishments from February 2020 to January 2022, who were recruited and interviewed during pregnancy or shortly after childbirth. They answered a questionnaire, underwent a physical examination and gave access to their antenatal care card information. BMI was calculated using maternal height, measured by the study team and self-reported pre-pregnancy weight measured at the first antenatal care visit. For 348/965 (36%) women, weight information was completed using self-reported data collected during the cohort baseline. Information about birth was obtained from the health centre's pregnancy surveillance system. Regression models were used to assess associations between C-section and BMI. Covariates that changed BMI estimates by at least 5% were included in the multivariable model. RESULTS: This study found that 121/965 (12.5%) women gave birth by C-section. Out of 495 women with pre-pregnancy normal weight, 46 (9.3%) had C-sections. Among the 335 women with pre-pregnancy overweight, 53 (15.5%) underwent C-sections, while 23 (18.5%) of the 124 with pre-pregnancy obesity had C-sections. After adjusting for age, parity, altitude, food and participation in a cash transfer programme pre-pregnancy overweight and obesity increased the odds of C-section by more than 80% (aOR 1.82; 95% CI 1.16-2.87 and aOR 1.85; 95% CI 1.02-3.38) compared to women with a normal BMI. CONCLUSIONS: High pre-pregnancy BMI is associated with an increased odds of having a C-section. Furthermore, our results suggest that high BMI is a major risk factor for C-section in this population. The effect of obesity on C-section was partially mediated by the development of preeclampsia, suggesting that C-sections are being performed due to medical reasons.

Implementation of a home blood pressure monitoring program for the management of hypertensive disorders of pregnancy, an observational study in British Columbia, Canada.

Background: COVID-19 pandemic has influenced health care delivery. We conducted an observational study to understand how obstetric medicine (ObM) physicians utilized home blood pressure monitoring (HBPM) to manage hypertension in pregnancy. Methods: Pregnant participants with risk factors or diagnosis of hypertensive disorders of pregnancy (HDP) were enrolled, May 2020-December 2021, and provided with validated home blood pressure (BP) monitor. ObM physicians completed questionnaires to elicit how home BP readings were interpreted to manage HDP. Results: We enrolled 103 people: 44 antepartum patients (33.5 ± 5 years, gestational age of 24 ± 5 weeks); 59 postpartum patients (35 ± 6 years, enrolled 6 ± 4 days post-partum). ObM physicians used range of home BP readings (70%) for management of HDP. Conclusions: HBPM to manage HDP is acceptable and can be used to manage hypertension during pregnancy. Further studies are needed to assess the generalizability of our findings and the safety of HBPM reliance alone in management of HDP.

Ventricular Tachycardia in Patients With Pre-eclampsia: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction Pre-eclampsia is a pregnancy-associated multisystem disorder; in rare cases, it can be complicated by arrhythmias such as ventricular tachycardia (VT). The purpose of this study was to determine the prevalence and predictors of VT among patients admitted with pre-eclampsia as well as to analyze the independent association of VT with in-hospital outcomes in this population. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. Patients with a primary diagnosis of pre-eclampsia were selected using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes. Subsequently, the study population was divided into patients who developed VT versus patients who did not develop this complication. We then assessed the predictors of VT in women with pre-eclampsia as well as the independent association of VT with outcomes taking into account confounders such as age, race, and comorbidities. Results Of 255,946 patients with pre-eclampsia, 92 developed VT (0.04%) during their hospital stay. Multivariate logistic regression showed that patients with VT were far more likely to develop cardiac arrest (adjusted odds ratio, or aOR: 92.582, 95% CI: 30.958-276.871, p=0.001), require permanent pacemaker implantation (aOR: 41.866, 95% CI: 14.800-118.432, p=0.001), develop postpartum hemorrhage (aOR: 2.932, 95% CI: 1.655-5.196, p=0.001), and require left heart catheterization (aOR: 19.508, 95% CI: 3.261-116.708, p=0.001). Predictors of VT included being African American (aOR: 1.939, 95% CI: 1.183-3.177, p=0.009), cerebrovascular disease (aOR: 23.109, 95% CI: 6.953-76.802, p=0.001), congestive heart failure (aOR: 50.340, 95% CI: 28.829-87.901, p=0.001), atrial fibrillation (aOR: 20.148, 95% CI: 6.179-65.690, p=0.001), and obstructive sleep apnea, or OSA (aOR: 3.951, 95% CI: 1.486-10.505, p=0.006). Patients in the VT cohort were found to have an increased length of hospital stay compared to the non-VT cohort (7.16 vs. 4.13 days, p=0.001). Conclusion In a large cohort of women admitted with pre-eclampsia, we found the prevalence of VT to be <1%. Predictors of VT included conditions such as atrial fibrillation, congestive heart failure, and OSA and being African American. VT was found to be independently associated with several adverse outcomes as well as an increased length of hospital stay.

The effect of maternal undernutrition on adverse obstetric outcomes among women who attend antenatal care in Gedeo zone public hospitals, cohort study design.

BACKGROUND: Undernutrition refers to an overall deficiency of nutrients due to an inadequate intake of a well-balanced diet. Undernourishment during pregnancy is an important contributor to maternal morbidity and mortality. It remains a persistent problem in developing countries, where women usually fall behind men in having access to food, health care, and education. Despite the high prevalence of maternal undernourishment, its direct impact on obstetric outcomes has not been studied in developing countries, including Ethiopia. OBJECTIVE: This study aimed to assess the effect of maternal undernutrition on adverse obstetric outcomes in Gedeo zone public hospitals. METHOD: A cohort study design was employed in Gedeo zone public hospitals from June 30, 2022, to February 28, 2023. This study included 721 pregnant women, 237 were exposed group whereas 484 were non-exposed. A systematic random sampling technique was used to select a non-exposed group and the exposed group was selected consecutively. Both groups were followed for 7 months, from 16 weeks of gestation to 24 h of delivery. The pretested interviewer-administered questionnaire and checklist were used. EpiData 4.4.1.2.version was used for data entry and analyzed using Stata version 16 software. A modified Poisson regression model with robust standard errors was used to determine relative risk, and the statistical association was declared at a p-value ≤ 0.05. Finally, the findings were reported in figures, tables, and words. RESULT: The incidence of adverse obstetrics outcomes among undernourished and normally nourished mothers was hypertensive disorder during pregnancy (HDDP) (7.49% vs. 3.19%), antepartum haemorrhage (7.49% vs. 3.19%), obstructed labor (1.53% vs. 3.49%), premature rupture of the membrane (2.5% vs. 3.33%), preterm labor (6.52% vs. 6.93%), instrumental vaginal delivery (1.8% vs. 4.3%), postpartum haemorrhage (5.95% vs. 3.88%), and sepsis (3.74% vs. 1.94%). The risk of adverse obstetric outcomes among undernourished women was hypertensive disorder during pregnancy (HDDP) (aRR) = 4.07, 95%CI: 2.53-6.55), antepartum haemorrhage (APH) (aRR = 5.0, 95% CI: 2.08-12.72), preterm labor (aRR = 1.8, 95%CI: 1.23-2.62), operative delivery (aRR = 1.24, 95%C: 0.87-1.78), postpartum haemorrhage (aRR = 3.02, 95%CI: 1.91-4.79), and sepsis/chrioaminitis (aRR = 3.55, 95%CI: 1.83-6.89) times higher than normally nourished women. CONCLUSION: The incidence rates of hypertensive disorder during pregnancy (HDDP), antepartum haemorrhage, postpartum haemorrhage, and sepsis were higher among undernourished women than normally nourished women. Undernourished women during pregnancy have an increased risk of adverse obstetrics outcomes including hypertensive disorder during pregnancy, antepartum, preterm labor, operative delivery, postpartum haemorrhage, and sepsis/chorioamnionitis.

Hepatic Rupture Associated With HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome: A Report of Two Cases and Literature Review.

Hepatic rupture is a rare complication of severe preeclampsia. A high index of suspicion is required in the presence of abdominal pain accompanied by hemodynamic decompensation in a pregnant woman. Hepatic rupture constitutes a medical emergency that demands immediate intervention, often with the support of other medical disciplines, in a highly specialized hospital setting. Unruptured hepatic hematomas can be managed conservatively. Immediate delivery and surgical repair of the liver are necessary for maternal survival. Spontaneous liver rupture in pregnancy is often unrecognized, highly lethal, and not completely understood with few cases having been reported in the literature. Therefore, we present two cases of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome with hepatic rupture, emphasizing their clinical presentation and therapeutic approaches.

A Case Report of Bilateral Exudative Retinal Detachment in Severe Pre-eclampsia.

We report a case of a 31-year-old gravida 2 para 1 female presenting to the optician with a two-week history of blurred vision and persistent headaches at 29 weeks gestation. Visual acuity on presentation was 6/100 in the right eye and 6/24 in the left eye. Fundoscopy of both eyes revealed serous retinal detachment in the absence of background retinal changes. On urgent admission to the maternity assessment unit, blood pressure was 189/126 mmHg and urine dipstick revealed 4+ proteinuria. Due to recurrent poor foetal heart rate variability on cardiotocography monitoring, an emergency caesarean was conducted. Sixteen hours following delivery, visual symptoms had improved, and clinical examination revealed normal blood pressure. An optical coherence tomography scan performed three months later was dry bilaterally with minor retinal pigment epithelium clumping. Serous retinal detachment involves the separation of the neurosensory retinal layer from the underlying retinal pigment epithelium. It is rare in pre-eclampsia but can be seen in patients with severe disease. The presentation of serous retinal detachment includes acute visual loss, reduced visual acuity, floaters, and flashing lights appearing in the vision. Although alarming on initial presentation, resolution is commonly seen within a couple of days postpartum. The pathogenic mechanism for serous retinal detachment development is widely discussed and thought to include changes to the choroidal circulation. Overall, although often self-resolving, a move to thorough antenatal care and vigilant monitoring in pre-eclamptic women is vital to prevent complications like this from occurring.

MicroRNAs in the Pathogenesis of Preeclampsia-A Case-Control In Silico Analysis.

Preeclampsia (PE) occurs in 5% to 7% of all pregnancies, and the PE that results from abnormal placentation acts as a primary cause of maternal and neonatal morbidity and mortality. The objective of this secondary analysis was to elucidate the pathogenesis of PE by probing protein-protein interactions from in silico analysis of transcriptomes between PE and normal placenta from Gene Expression Omnibus (GSE149812). The pathogenesis of PE is apparently determined by associations of miRNA molecules and their target genes and the degree of changes in their expressions with irregularities in the functions of hemostasis, vascular systems, and inflammatory processes at the fetal-maternal interface. These irregularities ultimately lead to impaired placental growth and hypoxic injuries, generally manifesting as placental insufficiency. These differentially expressed miRNAs or genes in placental tissue and/or in blood can serve as novel diagnostic and therapeutic biomarkers.

Detection of Urinary Misfolded Proteins for Imminent Prediction of Preeclampsia in Pregnant Women With Suspected Cases: Protocol for a Prospective Noninterventional Study.

BACKGROUND: Preeclampsia (PE) is one of the most common hypertensive diseases, affecting 2%-8% of all pregnancies. The high maternal and fetal mortality rates of PE are due to a lack of early identification of affected pregnant women that would have led to closer monitoring and care. Recent data suggest that misfolded proteins might be a promising biomarker for PE prediction, which can be detected in urine samples of pregnant women according to their congophilia (aggregated) characteristic. OBJECTIVE: The main purpose of this trial is to evaluate the value of the urine congophilia-based detection of misfolded proteins for the imminent prediction of PE in women presenting with suspected PE. The secondary objectives are to demonstrate that the presence of urine misfolded proteins correlates with PE-related maternal or neonatal adverse outcomes, and to establish an accurate PE prediction model by combining misfolded proteins with multiple indicators. METHODS: At least 300 pregnant women with clinical suspicion of PE will be enrolled in this prospective cohort study. Participants should meet the following inclusion criteria in addition to a suspicion of PE: ≥18 years old, gestational week between 20+0 and 33+6, and single pregnancy. Consecutive urine samples will be collected, blinded, and tested for misfolded proteins and other PE-related biomarkers at enrollment and at 4 follow-up visits. Clinical assessments of PE status and related complications for all participants will be performed at regular intervals using strict diagnostic criteria. Investigators and participants will remain blinded to the results. Follow-up will be performed until 42 days postpartum. Data from medical records, including maternal and fetal outcomes, will be collected. The performance of urine misfolded proteins alone and combined with other biomarkers or clinical variables for the prediction of PE will be statistically analyzed. RESULTS: Enrollment started in July 2023 and was still open upon manuscript submission. As of March 2024, a total of 251 eligible women have been enrolled in the study and enrollment is expected to continue until August 2024. Results analysis is scheduled to start after all participants reach the follow-up endpoint and complete clinical data are collected. CONCLUSIONS: Upon completion of the study, we expect to derive an accurate PE prediction model, which will allow for proactive management of pregnant women with clinical suspicion of PE and possibly reduce the associated adverse pregnancy outcomes. The additional prognostic value of misfolded proteins is also expected to be confirmed. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2300074878; https://www.chictr.org.cn/showproj.html?proj=202096. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54026.

Corrigendum: Serum D-dimer is not predictive of placenta-mediated complications in pregnancy at high risk: the multicentric prospective cohort AngioPred study.

[This corrects the article DOI: 10.3389/fcell.2023.1115622.].

Hypertensive disorders of pregnancy and long-term maternal cardiovascular risk: Bridging epidemiological knowledge into personalized postpartum care and follow-up.

Cardiovascular disease (CVD) is globally the leading cause of death and disability. Sex-specific causes of female CVD are under-investigated. Pregnancy remains an underinvestigated sex-specific stress test for future CVD and a hitherto missed opportunity to initiate prevention of CVD at a young age. Population-based studies show a strong association between female CVD and hypertensive disorders of pregnancy. This association is also present after other pregnancy complications that are associated with placental dysfunction, including fetal growth restriction, preterm delivery and gestational diabetes mellitus. Few women are, however, offered systematic cardio-preventive follow-up after such pregnancy complications. These women typically seek help from the health system at first clinical symptom of CVD, which may be decades later. By this time, morbidity is established and years of preventive opportunities have been missed out. Early identification of modifiable risk factors starting postpartum followed by systematic preventive measures could improve maternal cardiovascular health trajectories, promoting healthier societies. In this non-systematic review we briefly summarize the epidemiological associations and pathophysiological hypotheses for the associations. We summarize current clinical follow-up strategies, including some proposed by international and national guidelines as well as user support groups. We address modifiable factors that may be underexploited in the postpartum period, including breastfeeding and blood pressure management. We suggest a way forward and discuss the remaining knowledge gaps and barriers for securing the best evidence-based follow-up, relative to available resources after a hypertensive pregnancy complication in order to prevent or delay onset of premature CVD.