Search

Objective: Validation of blood pressure (BP) monitors in pregnant women are needed to ensure the accurate measurement of BP in pregnancy. Therefore the study aimed to evaluate the measurement accuracy of the G.LAB MD41A0 oscillometric automatic upper-arm blood pressure monitor in pregnancy and pre-eclampsia women according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018)., Methods: A total of 45 pregnant women were included in the cross-sectional validation study. The same left-arm sequential method was used for blood pressure measurement, and the blood pressure differences between the test device and the mercury standard reference were assessed according to the AAMI/ESH/ISO Universal Standard., Results: The participants included 15 normotensives, 15 gestational hypertension and 15 pre-eclampsia. The average (mean ± SD) differences between the device and mercury standard was -0.84±3.88 mmHg and -0.58±3.35 mmHg for systolic and diastolic blood pressure, respectively, for the validation Criterion 1. The SD of the averaged differences between the device and reference readings per participant was 2.92 mmHg and 2.28 mmHg for systolic and diastolic blood pressure, respectively, for the Criterion 2 of the universal standard., Conclusion: The G.LAB MD41A0 automatic upper-arm blood pressure monitor fulfills the criteria of the AAMI/ESH/ISO Universal Standard and can be recommended for clinical use and self-measurement in pregnancy and pre-eclampsia., Competing Interests: Y.W. was supported by the National Natural Science Foundation of China (No.82073663). Y.Z. was supported by the Natural Science Basic Research Project of Shaanxi Province (No.2020JM-659). There are no conflicts of interest., (© 2024 Zhang et al.)

Preeclampsia (PE) is characterized by de novo hypertension (HTN) and is often associated with intrauterine growth restriction (IUGR). Hallmarks of PE are placental ischemia, decreased nitric oxide (NO) bioavailability, oxidative stress (OS), and organ damage in the kidneys and brain. This study aims to characterize a new model of PE using pregnant IUGR rats from hypertensive placental ischemic dams. It is hypothesized that pregnant IUGR rats from hypertensive placental ischemic dams will have elevated blood pressure (BP), OS, and organ damage. In this study, pregnant rats are divided into two groups: normal pregnant (NP) and hypertensive placental ischemic dams (RUPP). Offspring from NP and RUPP dams were mated at 10 weeks of age to generate pregnant IUGR (IUGR Preg) and pregnant control (CON Preg) rats. BP and other markers of PE were evaluated during late gestation. Pregnant IUGR rats had elevated BP and systemic OS. The maternal body weight of pregnant IUGR rats and their pups' weights were decreased, while the brains were enlarged with elevated OS. In summary, pregnant IUGR rats, born from hypertensive placental ischemic dams, have HTN and increased systemic and brain OS, with larger brain sizes and smaller pups. Furthermore, this study shows that pregnant IUGR rats exhibit a preeclamptic-like phenotype, suggesting a new epigenetic model of PE., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Preeclampsia is a leading complication of pregnancy that lacks accurate tools for its early prediction. Improved risk stratification tools early in pregnancy would enable more efficient allocation of limited healthcare resources while ensuring that pregnant women destined to develop preeclampsia receive appropriate care. This brief perspective highlights the current state of first-trimester preeclampsia prediction. We focus on arterial stiffness, an important hemodynamic indicator of vascular health that has shown promising results for improved early prediction of preeclampsia by our and independent research groups. Further, we outline the promise, applicability, and feasibility of integrating arterial stiffness assessments into clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Calcium deficiency in women is strongly linked to an increased risk of developing preeclampsia. Mitochondrial calcium ([Ca 2+ ] m ) homeostasis is essential to regulate vascular smooth muscle cell (VSMC) function. However, the role of [Ca 2+ ] m in preeclampsia development remains largely unknown., Methods: To investigate this, human spiral arteries obtained from normotensive and preeclamptic women were collected for vascular function, RNA sequencing, and VSMC studies. N(ω)-nitro-L-arginine methyl ester-induced preeclampsia animal experiments were established to investigate the effects of intervening in [Ca 2+ ] m to improve the outcome for preeclamptic mothers or their infants., Results: Our initial findings revealed compromised vessel function in spiral arteries derived from patients with preeclampsia, as evidenced by diminished vasoconstriction and vasodilation responses to angiotensin II and sodium nitroprusside, respectively. Moreover, the spiral artery VSMCs from patients with preeclampsia exhibited phenotypic transformation and proliferation associated with the disrupted regulatory mechanisms of [Ca 2+ ] m uptake. Subsequent in vitro experiments employing gain- and loss-of-function approaches demonstrated that the mitochondrial Na + /Ca 2+ exchanger played a role in promoting phenotypic switching and impaired mitochondrial functions in VSMCs. Furthermore, mtNCLX (mitochondrial Na + /Ca 2+ exchanger) inhibitor CGP37157 significantly improved VSMC phenotypic changes and restored mitochondrial function in both patients with preeclampsia-derived VSMCs and the preeclampsia rat model., Conclusions: This study provides comprehensive evidence supporting the disrupted regulatory mechanisms of [Ca 2+ ] m uptake in VSMCs of spiral arteries of patients with preeclampsia and further elucidates its correlation with VSMC phenotypic switching and defective spiral artery remodeling. The findings suggest that targeting mtNCLX holds promise as a novel therapeutic approach for managing preeclampsia., Competing Interests: None.

Background: Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia., Methods: To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1., Results: The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor., Conclusions: The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications., Competing Interests: None.

Preeclampsia (PE) is associated with increased angiotensin II sensitivity and poor neurological outcomes marked by temporal loss of neural control of blood pressure. Yet the role of centrally expressed angiotensin II type 1 receptor (AT1R) within the paraventricular nucleus of the hypothalamus (PVN) in the PE model is not understood. In a PE rat model with reduced placental perfusion pressure (RUPP) induced on gestational day 14 (GD14), the PVN expression and cellular localization of AT1R were assessed using immunofluorescence and western blotting. The sensitivity of RUPP to acute angiotensin II infusion was assessed. AT1R was antagonized by losartan (100 µg/kg/day) for 5 days intracerebroventricularly (ICV). Hemodynamic data and samples were collected on GD19 for further analysis. RUPP upregulated (p < 0.05) mRNA and protein of AT1R within the PVN and lowered (p < 0.05) circulating angiotensin II in rats. RUPP increased neural and microglial activation. Cellular localization assessment revealed that AT1R was primarily expressed in neurons and slightly in microglia and astrocytes. Infusion of 100 ng/kg as bolus increased the mean arterial pressure (MAP in mmHg) in both RUPP and Sham. ICV losartan infusion attenuated RUPP-increased MAP (113.6 ± 6.22 in RUPP vs. 92.16 ± 5.30 in RUPP + Los, p = 0.021) and the expression of nuclear transcription factor NF-κB, tyrosine hydroxylase (TH), NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) in the PVN. Our data suggest that centrally expressed AT1R, within the PVN, contributes to placental ischemia-induced hypertension in RUPP rats highlighting its therapeutic potential in PE., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women., Methods: The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta., Results: 1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p ​< ​0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p ​= ​0.12)., Conclusions: Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter., Competing Interests: Declaration of competing interest After initiation of this work, ASE has been employed by Novo Nordisk A/S; Novo Nordisk A/S is not involved in this project. PES reports consulting fees from Novo Nordisk A/S outside the submitted work. Not relevant to the study FG discloses honoraria: Advisor (Bayer, Abbott, Boehringer-Ingelheim, Pfizer, Alnylam, Ionis, Pharmacosmos, Amgen), speakers fee (Orion Pharma, Astra-Zeneca). Dr KFK has received research grants from AP Møller og hustru Chastine McKinney Møllers Fond, The John and Birthe Meyer Foundation, Research Council of Rigshopitalet, The University of Copenhagen, The Danish Heart Foundation, The Lundbeck Foundation, The Danish Agency for Science, Technology and Innovation by The Danish Council for Strategic Research, Novo Nordisk Foundation. KFK is on the Speakers Bureau of Canon Medical Systems. LK reports speakers fee from Astra Zeneca, Bayer, Boehring, Novartis and Novo. The remaining authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic hypertension (CH) during pregnancy, identified before or within the first 20 weeks, presents varying risks depending on the timing of diagnosis. This real-world study was conducted from January 2018 to June 2023 and included singleton pregnancies with CH to compare pre-pregnancy CH (Group 1) and newly diagnosed CH (Group 2). There were 565 women in the final analysis, with 307 in Group 1 with pre-pregnancy CH and 258 in Group 2 with new-onset CH. Those in Group 1 more frequently had pre-gestational diabetes and a history of hypertensive disorders in pregnancy, whereas Group 2 had a higher incidence of excessive gestational weight gain. Notably, 56.2% of Group 2 patients did not receive antihypertensive treatment before 20 weeks, while the proportion was 36.2% in Group 1, resulting in a significant difference in baseline blood pressure. The study revealed higher incidences of preterm preeclampsia (44.2% vs. 34.9%) and placental abruption (5.4% vs. 2.0%) in Group 2 compared to Group 1. After adjustment, logistic regression indicated that Group 2 had a 1.8-fold higher risk of preterm preeclampsia than Group 1. These findings suggest that pregnant women newly diagnosed with CH in the first 20 weeks face increased adverse outcomes compared to those diagnosed before pregnancy. Intense monitoring and earlier intervention may help manage women with new-onset CH., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Preeclampsia is associated with intrauterine growth restriction (IUGR), which can lead to impaired postnatal growth and neurodevelopment in preterm infants. Preeclampsia can also occur without IUGR and its impact on postnatal nutrition, growth, and body composition remains not fully investigated to the best of our knowledge., Methods: This study included infants born before 37 weeks of gestation who underwent air displacement plethysmography to measure body composition (fat-free mass [FFM] and fat mass [FM]) at term-equivalent age. We compared infants born to mothers with preeclampsia and IUGR (PE-IUGR group) and preeclampsia without IUGR (PE-non-IUGR group) to those born to mothers without preeclampsia (control group)., Results: In total, 291 infants were enrolled (control: n = 227; PE-non-IUGR: n = 43; PE-IUGR: n = 21). FFM was significantly lower in the PE-IUGR (mean differences -231 g (IQR: (-373, -88); p < 0.001)) and PE-non-IUGR groups (mean differences -260 g (IQR: (-372, -149); p < 0.001)) in comparison to the control group. FM was not significantly different between the three groups., Conclusions: This study indicates that infants of preeclamptic mothers, even without IUGR, had significantly lower FFM at term-equivalent age compared to the control group. Further research is necessary to determine if these variations can be modified.

Gestational hypertension (GH) and preeclampsia (PE) are associated with the onset of hypertension. This study aimed to investigate whether the blood pressure (BP) pattern in GH is associated with the prevalence of hypertension later in life. In this prospective cohort study pregnant women screened for GH underwent medical history, laboratory analysis, ambulatory blood pressure monitoring (AMBP), and transthoracic echocardiography (with left ventricular global longitudinal strain (LVGLS)) assessment. Overall, 138 GH (67 non-dippers and 71 dippers), 55 preeclamptic, and 72 normotensive pregnant controls were included. Women were followed in the postpartum period, first after 6 weeks and later on, for the occurrence of hypertension. The median follow-up was 8.97 years (8.23; 9.03). Non-dippers and PE compared with normotensives and dippers had a higher prevalence of hypertension onset ( p < 0.01), as well as significantly reduced absolute values of LVGLS during pregnancy, after delivery, and at the time of onset of hypertension during follow-up ( p < 0.01). Night-time diastolic BP, LVGLS, age, and left ventricular ejection fraction were the strongest predictors of postpartum onset of hypertension. The non-dipping BP pattern in GH was significantly associated with the onset of hypertension later in life, as well as with decreased systolic function.

Background: Whether cardiovascular dysfunction is associated with preeclampsia in women without fetal growth restriction (FGR) is unclear. Our objective was to investigate associations between third-trimester cardiac output (CO) and systemic vascular resistance and risk of hypertensive disorders of pregnancy in women with and without FGR., Methods and Results: A case-cohort study in 906 pregnant women in Denmark with repeated third-trimester cardiac function assessments was performed using the Ultrasound Cardiac Output Monitor 1A. Using Cox regression, we compared rates of hypertensive disorders of pregnancy in women with low, normal, and high CO and normal and high systemic vascular resistance, by FGR status and gestational age, and evaluated associations between a third-trimester drop in CO or increase in systemic vascular resistance and preeclampsia risk in women without FGR. The analysis included 249 women with preeclampsia (42 with FGR) and 119 women with gestational hypertension. Low CO was strongly associated with preeclampsia at <37 weeks (women with FGR: hazard ratio [HR], 5.25 [95% CI, 1.26-21.9]; women without FGR: HR, 2.19 [95% CI, 1.07-4.48]). Our results also suggested an association between low CO and preeclampsia at ≥37 weeks among women without FGR (HR, 1.31 [95% CI, 0.84-2.03]), and between a third-trimester drop in CO >75th percentile and preeclampsia in women without FGR (odds ratio, 1.91 [95% CI, 0.84-4.36]). High systemic vascular resistance was strongly associated with increased rates of all forms of hypertensive disorders of pregnancy., Conclusions: Low CO is associated with preeclampsia risk in women with and without FGR, particularly before 37 weeks. Repeated measurements of third-trimester cardiovascular function might identify women without FGR for monitoring for preeclampsia, but this result needs to be confirmed in other studies.

Preeclampsia (PE) is a multisystem pregnancy disorder characterized by impaired remodeling of placental spiral arteries, which leads to the release of pro-inflammatory cytokines and anti-angiogenic agents. However, treatment options for PE are limited, with termination of pregnancy being the only curative option. In this work, we investigated the effects of human amniotic epithelial cells (hAECs) in PE rat model. The rats were induced with lipopolysaccharide (LPS) on gestational day 14.5 followed by injection of hAECs and human umbilical cord mesenchymal stem cells 24 h later. The hAECs treatment resulted in a reduction in blood pressure and proteinuria in the PE rat model. Furthermore, hAECs treatment decreased levels of pro-inflammatory cytokines, reduced inflammatory cells aggregation, and alleviated the damage to placental spiral arteries by downregulating the expression of anti-angiogenic factor and upregulating proangiogenic factor. In vitro experiments confirmed that hAECs treatment restored the proliferation, migration, and angiogenesis of LPS-damaged human umbilical vein endothelial cells. Additionally, hAECs treatment had positive effects on fetal weight and neurological development in the PE group, with no negative effects on the physical development or fertility of offspring rats. These results suggested that hAECs transplantation may be a novel adjuvant therapeutic strategy for PE by reducing the inflammatory and enhancing placental spiral artery angiogenesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Preeclampsia, a pregnancy disorder characterized by de novo hypertension and maternal multisystem organ dysfunction, is the leading cause of maternal mortality worldwide and is associated with a fourfold greater risk of cardiovascular disease throughout the lifespan. Current understanding of the etiology of preeclampsia remains unclear, due in part to the varying phenotypical presentations of the disease, which has hindered the development of effective and mechanism-specific treatment or prevention strategies both during and after the affected pregnancy. These maternal sequelae of preeclampsia are symptoms of systemic vascular dysfunction in the maternal nonreproductive microvascular beds that drives the development and progression of adverse cardiovascular outcomes during preeclampsia. Despite normalization of vascular disturbances after delivery, subclinical dysfunction persists in the nonreproductive microvascular beds, contributing to an increased lifetime risk of cardiovascular and metabolic diseases and all-cause mortality. Given that women with a history of preeclampsia demonstrate vascular dysfunction despite an absence of traditional CVD risk factors, an understanding of the underlying mechanisms of microvascular dysfunction during and after preeclampsia is essential to identify potential therapeutic avenues to mitigate or reverse the development of overt disease. This article aims to provide a summary of the existing literature on the pathophysiology of maternal microvascular dysfunction during preeclampsia, the mechanisms underlying the residual dysfunction that remains after delivery, and current and potential treatments both during and after the affected pregnancy that may reduce microvascular dysfunction in these high-risk women. © 2024 American Physiological Society. Compr Physiol 14:5703-5727, 2024., (Copyright © 2024 American Physiological Society. All rights reserved.)

Computational models can be at the basis of new powerful technologies for studying and classifying disorders like pre-eclampsia, where it is difficult to distinguish pre-eclamptic patients from non-pre-eclamptic based on pressure when patients have a track record of hypertension. Computational models now enable a detailed analysis of how pregnancy affects the cardiovascular system. Therefore, new non-invasive biomarkers were developed that can aid the classification of pre-eclampsia through the integration of six different measured non-invasive cardiovascular signals. Datasets of 21 pregnant women (no early onset pre-eclampsia, n = 12; early onset pre-eclampsia, n = 9) were used to create personalised cardiovascular models through computational modelling resulting in predictions of blood pressure and flow waveforms in all major and minor vessels of the utero-ovarian system. The analysis performed revealed that the new predictors PPI (pressure pulsatility index) and RI (resistance index) calculated in arcuate and radial/spiral arteries are able to differentiate between the 2 groups of women (t-test scores of p < .001) better than PI (pulsatility index) and RI (Doppler calculated in the uterine artery) for both supervised and unsupervised classification. In conclusion, two novel high-performing biomarkers for the classification of pre-eclampsia have been identified based on blood velocity and pressure predictions in the smaller placental vasculatures where non-invasive measurements are not feasible., (© 2024. The Author(s).)

Preeclampsia (PE) is a severe pregnancy complication characterized by significant alterations in coagulation function. This study aims to analyze the correlation between coagulation function, platelet parameters, and pregnancy outcomes in PE patients. Clinical data, along with blood and urine samples, were collected from 168 PE patients and 128 healthy pregnant women. General demographic and laboratory testing data were recorded, and maternal and fetal outcomes were followed up. Data were analyzed using Kaplan-Meier and logistic regression analyses. In mild PE patients, thrombin time (p = .000), platelet distribution width (PDW) (p = .000), and clot formation time (p = .000) were increased, while prothrombin time (p = .000) and fibrinogen (p = .045) were reduced. With increasing PE severity, prothrombin time (p = .000), platelet count (PLT) (p = .000), mean platelet volume (MPV) (p = .000), plateletcrit (p = .000), maximum amplitude (MA) (p = .000), and coagulation index (p = .001) decreased, whereas activated partial thromboplastin time (APTT) (p = .000), thrombin time (p = .002), D-dimer (p = .026), and PDW (p = .000) increased. Lower prothrombin time (p = .048), PLT (p = .004), and coagulation index (p = .026) or higher APTT (p = .032), thrombin time (p = .044), D-dimer (p = .023), and PDW (p = .016) were associated with a higher risk of poor pregnancy outcomes. Thrombin time was identified as an independent risk factor (p = .025, OR = 2.918, 95% CI: 1.145-7.436), whereas gestational age was an independent protective factor (p = .000, OR = 0.244, 95% CI: 0.151-0.395). This study demonstrates that specific coagulation and platelet parameters are significantly associated with PE severity and adverse pregnancy outcomes. These findings highlight the importance of monitoring coagulation function in PE patients to improve clinical management and outcomes., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Preeclampsia is a hypertensive disorder of pregnancy marked by vascular dysfunction, large artery stiffness, and excess oxidized low-density lipoprotein (oxLDL). oxLDL activates oxidative stress pathways which contribute to arterial stiffness through interaction with the lectin-like oxLDL receptor 1 (LOX-1). Increased vascular stiffness is associated with higher pulse wave velocity and downstream microvasculature damage. Here we evaluated the ability of LOX-1 inhibition (LOX-1i) to prevent large artery structural and microvascular structural and functional changes via assessment of the descending thoracic aorta (DTAo) and posterior cerebral arteries (PCA) in a high cholesterol model of preeclampsia. Adult female Sprague Dawley normal late-pregnant (LP) and experimentally preeclamptic (ePE, high cholesterol diet d7-19) animals underwent intraperitoneal (i.p.) implantation of a mini-osmotic pump at d12 containing LOX-1 neutralizing antibodies (ePE + LOX-1i, n = 7) or goat IgG as vehicle control (LP + IgG, n = 8 and ePE + IgG, n = 8). Animals were studied at d19. DTAos and PCAs were removed for histologic assessment and isolated vessel experiments, respectively. Fetuses and placentas were weighed individually. Plasma was analyzed for markers of oxidative stress. ePE + IgG DTAo elastin content (an indirect metric of stiffness) was not significantly different from the LP + IgG group. Nonetheless, trending elastin break and sinuosity data (higher number of breaks and lower sinuosity in the ePE + IgG group compared to LP + IgG) suggested increased stiffness in this high cholesterol PE model. LOX-1i appeared to prevent a decrease in elastin. PCAs showed no structural changes with ePE or LOX-1i. ePE PCAs had increased reactivity to the nitric oxide donor sodium nitroprusside and decreased tone that was unaffected by LOX-1i. ePE animals had increased plasma oxLDL and 3-nitrotyrosine that was unaffected by LOX-1i. Taken together, LOX-1i may improve large artery stiffness without mitigation of the oxidative stress or cerebral microvascular dysfunction seen in ePE. Understanding these mechanisms is important in abating the long-term risks of preeclampsia., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The aim of the study is to analyze ventricular-vascular properties with different ventricular-arterial coupling (VAC) ratio in the preeclamptic women. Seventy-seven pregnant women with preeclampsia and eighty-nine with normal pregnancy were performed echocardiography. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees). Using the VAC value of 0.8 as the cut-off near uncoupling, the preeclampsia cases were divided into two subgroups: VAC ratio ≥ 0.8 and <0.8. Cardiac structure and function, VAC properties, as well as four components of the LV pressure-strain loop, including global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were determined. The preeclampsia with VAC ≥ 0.8 had an enlarger indexed ventricular volume and a thicker relative ventricular wall than the VAC < 0.8. The Ees significantly increased in the subgroup with VAC < 0.8 and decreased in the VAC ≥ 0.8, while the Ea increased in both of them. The preeclampsia with VAC ≥ 0.8 showed an obvious augmentation in GWI, GCW and GWE, along with a similar GWW compared to those with VAC < 0.8. There were variable relationships between the LV pressure-strain components and VAC properties. Thus, the preeclampsia with VAC ≥ 0.8 undergoes a more adverse remodeling and a greater impact on cardiac contractility. The increased stiffness of the heart and arterial system, and increased resistance of peripheral vessels net lead to the deteriorative ventricular efficiency with elevated myocardial oxygen consumption during a preeclampsia pregnancy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The aim of the study was to examine the association between prenatal exposure to maternal Hypertensive disorder during pregnancy (HDP) on brain structure and neurocognitive functioning (NCF) in singleton children aged between 9 and 10 years using the baseline wave of the Adolescent Brain and Cognitive Development (ABCD) Study. The ABCD Study ® interviewed each child (and their parents), measured NCF, and performed neuroimaging. Exposure to maternal high blood pressure (HBP) and preeclampsia or eclampsia (PE/EL) were extracted from the developmental history questionnaire. Differences in cortical thickness (CTh) and five cognitive abilities (two executive functions, working and episodic memory, processing speed, and two language abilities) between exposed and unexposed children were examined using generalized linear models. The mediating effects of CTh, birthweight, and BMI on the relationship between maternal HDP on NCF were also examined. A total of 584-children exposed to HBP, 387-children exposed to PE/EL, and 5,877 unexposed children were included in the analysis. Neither CTh nor NCF differed between the exposed and unexposed children with or without adjusting for the confounders including the child's age, sex, race, education, and birth histories. The whole-brain CTh did not mediate the relationships between HDP and NCF. However, the relationship between HDP and most of the NCF was mediated by the child's birthweight and BMI. Exposure to maternal HDP can affect their offspring's later-life cognitive abilities via low birthweight and BMI during childhood. Prospective longitudinal studies, following up from infancy, are needed to further delineate the association of HDP on children's cognitive abilities.

Preeclampsia is a common pregnancy complication affecting 5% to 7% of all pregnancies worldwide annually. While the pathogenesis is not fully understood, maternal endothelium dysfunction is thought to be a central component to preeclampsia development. Studies to dissect maternal endothelial dysfunction, particularly on a patient-specific basis, are hampered by limited access to systemic primary endothelial cells (ECs). The objective of this study was to establish a replenishable, patient-specific in vitro EC model to allow robust mechanistic studies to dissect endothelial dysfunction in preeclampsia. Induced pluripotent stem cells (iPSCs) from three women with a history of normotensive pregnancies were differentiated into ECs. The established ECs were exposed to pooled sera from normotensive pregnancies, preeclamptic pregnancies, normotensive postpartum for non-pregnant comparison and controls. Endothelial functions including nitric oxide (NO) release, cell migration, tube formation and viability were evaluated. Levels of NO release were significantly lower after incubation with preeclamptic sera compared to the fetal bovine serum (FBS) control, and normotensive and non-pregnant (postpartum) sera treatments were also lower than FBS but higher than preeclamptic sera treatments. Tube formation and cell migration were also impaired with preeclamptic sera compared to FBS controls. Cell viabilities remained unaffected by any sera treatment. Consistent outcomes were obtained across all three patient-specific lines treated with the same pooled sera. Establishment of patient-derived iPSC-ECs treated with pregnancy sera serves as a novel model to explore the interplay between individual maternal endothelial health and circulating factors that lead to endothelial dysfunction in preeclampsia., (© 2024. The Author(s).)

Hypertensive disorders of pregnancy (HDP), such as preeclampsia and eclampsia, present significant risks to maternal and fetal health. While immediate complications are well-documented, emerging research highlights potential neurocognitive impacts on both mothers and their offspring. This narrative review synthesizes evidence on these neurocognitive outcomes associated with HDP, focusing on preeclampsia and eclampsia. A literature search was conducted for studies published from 2000 to February 2024. Maternal outcomes, including memory, executive function, and psychosocial well-being, were assessed across 11 studies, while fetal and neonatal neurocognitive outcomes were explored in five studies. Consistent findings indicate that preeclampsia and eclampsia are linked to impairments in maternal cognitive functions and psychosocial health. Offspring exposed to these conditions in utero also show cognitive deficits and alterations in brain connectivity. Contributing factors include placental dysfunction, altered angiokine levels, maternal stress, and socioeconomic variables. To mitigate these impacts, future research should focus on clarifying the underlying mechanisms and developing early interventions. This review emphasizes the necessity of multidisciplinary approaches to improve neurocognitive outcomes for both mothers and their children affected by preeclampsia and eclampsia., (© 2024. The Author(s).)

Objectives: To determine the prevalence of proteinuria in patients diagnosed with intrahepatic cholestasis of pregnancy (IHCP), and the association between the presence of proteinuria and adverse pregnancy outcomes., Methods: This was a retrospective cohort study. The study included all pregnant patients between July 2014 and January 2022, at gestational age > 24weeks who had been diagnosed with IHCP and had completed a 24-hour protein collection. High order multifetal gestations were excluded. Patients were divided into 3 groups:1. IHCP without proteinuria (Non-proteinuric group);2. IHCP with proteinuria and normal blood pressure (Isolated proteinuria group), and 3. IHCP with proteinuria and elevated blood pressure (IHCP with preeclampsia (PET)). Primary outcome was defined as a composite maternal-fetal outcome including: preterm labor <34 weeks, arterial cord blood ph<7.1, rate of Cesarean delivery due to non-reassuring fetal monitoring. Parametric and non-parametric statistical methods were used for analysis., Results: A total of 272 met all inclusion criteria and were included, 94 patients (34.5%) had proteinuria; of them, 67 (24.6%) had isolated proteinuria and 27 (9.9%) had PET. Demographic parameters were comparable among the groups. Patients with PET had higher rates of in-vitro fertilization (IVF) treatments, twin gestation and elevated serum creatinine and urea levels. The rate of composite adverse pregnancy outcome was higher in patients with PET compared with patients with and without proteinuria (14/27 (51.9%) vs. 18/67 (26.9%) vs. 49/178 (27.5%), respectively, p = 0.03)., Conclusions: Approximately 35% of patients with IHCP have proteinuria. The presence of PET, rather than isolated proteinuria, is associated with adverse pregnancy outcome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Watad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The goal of our research is to elucidate and better assess placental function in rats with preeclampsia through an innovative application of ultrasound-based radiomics. Using a rat model induced with L-NAME, we carefully investigated placental dysfunction via microstructural analysis and immunoprotein level assessment. Employing the Boruta feature selection method on ultrasound images facilitated the identification of crucial features, consequently enabling the development of a robust model for classifying placental dysfunction. Our study included 12 pregnant rats, and thorough placental evaluations were conducted on 160 fetal rats. Distinct alterations in placental microstructure and angiogenic factor expression were evident in rats with preeclampsia. Leveraging high-throughput mining of quantitative image features, we extracted 558 radiomic features, which were subsequently used to construct an impressive evaluation model with an area under the receiver operating curve (AUC) of 0.95. This model also exhibited a remarkable sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 88.7%, 91.5%, 90.2%, 90.4%, and 90.0%, respectively. Our findings highlight the ability of ultrasound-based radiomics to detect abnormal placental features, demonstrating its potential for evaluating both normative and impaired placental function with high precision and reliability., (© 2024. The Author(s).)

To analyze the possible association between serum uric acid (SUA) and nocturnal hypertension and to evaluate the ability of these variables (alone or in combination) to predict preeclampsia (PE) we conducted a historical cohort study in 532 high-risk pregnancies. Women were divided according to SUA values and nocturnal blood pressure (BP) into four groups: 1- normal SUA and nocturnal normotension; 2- high SUA and nocturnal normotension; 3- normal SUA and nocturnal hypertension and 4- high SUA and nocturnal hypertension. High SUA was defined by the top quartile values and nocturnal hypertension as BP ≥ 120/70 mmHg, using ambulatory blood pressure monitoring (ABPM), during nocturnal rest. Risks for PE were compared using logistic regression. SUA had a weak but significant correlation with daytime systolic ABPM (r = 0.11, p = 0.014), daytime diastolic ABPM (r = 0.13, p = 0.004), nighttime systolic ABPM (r = 0.16, p < 0.001) and nighttime diastolic ABPM (r = 0.18, p < 0.001). Also, all ABPM values were higher in women with high SUA. The absolute risk of PE increased through groups: 6.5%, 13.1%, 31.2%, and 47.9% for groups 1, 2, 3, and 4, respectively, p < 0.001. Compared with Group 1, Group 3 (OR 6.29 95%CI 3.41-11.60), but not Group 2 (OR 2.15 95%CI 0.88-5.24), had statistically significant higher risk for PE. Group 4 (women with both, high SUA and nocturnal hypertension) had the highest risk (OR 13.11 95%CI 6.69-25.70). Risks remained statistically significant after the adjustment for relevant variables. In conclusion, the combination of SUA > 4 mg/dL and nocturnal BP > 120/70 mmHg implies a very high risk to developed PE., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Preeclampsia (PE) is a multisystemic disorder of pregnancy that not only causes perinatal mortality and morbidity but also has a long-term toll on the maternal and fetal cardiovascular system. Women diagnosed with PE are at greater risk for the subsequent development of hypertension, ischemic heart disease, cardiomyopathy, cerebral edema, seizures, and end-stage renal disease. Although PE is considered heterogeneous, inefficient extravillous trophoblast (EVT) migration leading to deficient spiral artery remodeling and increased uteroplacental vascular resistance is the likely initiation of the disease. The principal pathophysiology is placental hypoxia, causing subsequent oxidative stress, leading to mitochondrial dysfunction, mitophagy, and immunological imbalance. The damage imposed on the placenta in turn results in the "stress response" categorized by the dysfunctional release of vasoactive components including oxidative stressors, proinflammatory factors, and cytokines into the maternal circulation. These bioactive factors have deleterious effects on systemic endothelial cells and coagulation leading to generalized vascular dysfunction and hypercoagulability. A better understanding of these metabolic factors may lead to novel therapeutic approaches to prevent and treat this multisystemic disorder. In this review, we connect the hypoxic-oxidative stress and inflammation involved in the pathophysiology of PE to the resulting persistent cardiovascular complications in patients with preeclampsia.

Objective: To determine if the relationship between blood pressure (BP) before 16 weeks' gestation and subsequent onset of preeclampsia differs by parity, and by history of hypertensive disorders of pregnancy (HDP) in parous women., Study Design: Data from two studies were pooled. First, routinely collected clinical data from three metropolitan hospitals in Sydney, Australia (2017-2020), where BP was measured as part of routine clinical care using validated mercury-free sphygmomanometers. Second, prospectively collected research data from the INTERBIO-21st Study, conducted in six countries, investigating the epidemiology of fetal growth restriction and preterm birth, where BP was measured by dedicated research staff using an automated machine validated for use in pregnancy., Main Outcome: Adjusted odds ratios (aOR) (95% confidence interval (CI)) for the association of systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) with preeclampsia were obtained from logistic regression models. Models were adjusted for age, smoking, body mass index, previous hypertension, previous diabetes, and previous preeclampsia. Interactions for parity, and history of HDP in parous women were included., Results: There were 14,086 pregnancies (Sydney = 11008, INTERBIO-21st = 3078) in the pooled analyses, 6914 (49 %) were parous, of which 414 (6.0 %) had a history of HDP. Nulliparous women had a higher risk of preeclampsia (2.6 %) compared with parous women (1.5 %): [aOR (95 %CI) 3.61 (2.67, 4.94)], as did parous women with a history of HDP (15.0 %) compared with no history (0.7 %) [12.70 (8.02, 20.16)]. MAP before 16 weeks' gestation (mean [SD] 78.8[8.6] mmHg) was more strongly associated than SBP or DBP with development of preeclampsia in parous women [2.22 (1.81, 2.74)] per SD higher MAP] compared with nulliparous women [1.58 (1.34, 1.87)] (p for interaction 0.013). There were no significant differences on the effect of blood pressure on preeclampsia in parous women by history of HDP (p for interaction 0.5465)., Conclusion: The risk of preeclampsia differs according to parity and history of HDP in a previous pregnancy. Blood pressure in early pregnancy predicts preeclampsia in all groups, although more strongly associated in parous than nulliparous women, but no different in parous women by history of HDP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Preeclampsia is a multisystem disorder associated with defective trophoblast invasion, maternal syndrome, and capillary endothelial leak. The presence of ascites/third space fluid accumulation increases the risk of maternal morbidity and mortality. The current criteria/guidelines of preeclampsia do not establish the presence of ascites as a marker of severity or recognize the timing and need for early delivery despite associated complications. Medline and Embase databases were searched to identify relevant literature, reported up to December 2023, regarding the pathophysiology, pregnancy outcome, and management of preeclampsia complicated with ascites. A total of 5 studies on pathophysiology and eight on pregnancy outcomes met the inclusion criteria, with 41 case reports on ascites in preeclampsia. The etiopathogenesis for the development of ascites in preeclampsia includes endothelial damage, capillary hyperpermeability, release of vasoconstrictive agents, reduced intravascular oncotic pressure, and raised intraabdominal pressure. The presence of ascites represents the extreme form of microvascular damage, which also correlates with the raised sFlt-1 levels in this condition. The adverse pregnancy outcomes include increased risk of congestive heart failure, eclampsia, renal failure, disseminated intravascular coagulation, acute respiratory distress syndrome, and maternal death. The presence of ascites in preeclampsia is associated with the deterioration of the maternal condition. Hence, it is indicative of preeclampsia with severe features and requires vigilant monitoring, and prompt delivery may be considered., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Pregnancy complications related to hypertension can affect both mother and newborn. Pulse wave attenuation (PWA) captured through fingertip photoplethysmography (PPG) provide valuable insights into maternal acute hemodynamic and autonomic vascular function. Here, we quantify the nocturnal dynamics of PWA during early pregnancy and assess their association with the development of gestational hypertension, preeclampsia and gestational diabetes., Methods: PWA dynamics were assessed on overnight polysomnography-derived PPG signals from a cohort of 2714 pregnant women (mean age: 26.8 ± 5.5 years) enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). We determined the average duration (PWA duration ) and depth (PWA depth ) of PWA events in all women., Results: Odds ratio (OR) analysis-adjusted common confounders indicates that an average PWA duration greater than 8.74 s was associated with the increased risk of gestational hypertension [OR = 1.75 (1.27-2.39), P  < 0.001]. Similarly, average PWA depth greater than 1.19 was associated with an increased risk of preeclampsia [OR = 1.53 (1.01-2.33), P  = 0.045] and gestational diabetes [OR = 1.66 (1.01-2.73), P  = 0.044]., Conclusion: PWA attenuation dynamics during early pregnancy predict the risk of developing gestational hypertension and diabetes condition for women in their later trimesters. Potentially obtainable from smart wearable consumer devices, PWA analysis offers a low-cost, accessible and scalable marker that can enhance the management of pregnancy-induced cardiometabolic issues., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of the present study is to identify the impact of the postpartum menstrual cycle on aldosterone, renin, and their ratio of women with and without a preeclamptic pregnancy in the past. To this end, we analysed the data from 59 women with a history of preeclampsia and 39 healthy parous controls. Five to seven months post-partum, we measured aldosterone, renin, and the aldosterone-to-renin ratio during both the follicular and the luteal phase of the menstrual cycle. All measurements were taken in the supine position in the morning. Patients had maintained a standardized sodium diet in the week prior to the measurements. Our results show that in both post-partum women with recent preeclampsia and controls, average levels of renin and aldosterone are significantly elevated in the luteal phase as compared to the follicular phase. The aldosterone-to-renin ratio does not differ between the two phases in either group. Compared to controls, women with recent preeclampsia have significantly lower levels of renin, aldosterone, and aldosterone-to-renin ratio in the follicular phase. This remained consistent in the luteal phase, except for renin. A close correlation existed between the luteal and follicular aldosterone-to-renin ratio in the control group but not in the preeclampsia group. We conclude that both renin and aldosterone are significantly affected by the menstrual cycle whereas the resulting aldosterone-to-renin ratio is not. Post-partum women with recent preeclampsia tend to have lower values for aldosterone and the aldosterone-to-renin ratio than controls., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH)., Study Design: This prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated., Main Outcome Measure: The role of CPUR in predicting CAPO in preeclampsia and gestational hypertension., Results: The CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001)., Conclusion: CPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na + ) evokes beneficial placental signals that are disrupted in preeclampsia., Methods: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na + concentrations., Results: Women with preeclampsia had reduced placental and urinary Na + concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na + exposure. Mechanistically, inhibiting Na + /K + -ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it., Conclusions: Enhanced Na + availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable., Competing Interests: None.

Background: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs preeclamptic pregnancies., Methods: Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum., Results: Recruited subjects (n = 68) were grouped according to their blood pressure as: a) normotensive pregnancy n = 15; b) PreE with normotensive postpartum (PreE-Resolved, n = 36); c) PreE with persistent postpartum HTN (PreE-HTN, n = 17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], P < .001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, P < .001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, P < .001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, P = .001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, P = .045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, P = 0.045). Exercise duration was negatively associated with gravidity (R = -0.27, P = .029) and postpartum LV mass index (R = -0.45, P < .001), resting average E/e' (R = -0.51, P < .001), BMI (R = -0.6, P < .001) and resting SBP (R = -0.51, P < .001)., Conclusions: Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors., Competing Interests: Conflict of interest None reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Endothelial dysfunction (ED) plays a prominent role in the pathogenesis of preeclampsia (PE). There is a need for non-invasive methods to assess endothelial function in preeclamptic patients. In the present study, adropin, autotaxin (ATX), and lysophosphatidic acid (LPA) were evaluated as indicators of ED. Patients diagnosed with PE and healthy pregnant women (n = 42 for each group) were compared. After measuring flow-mediated dilation (FMD), the participants were stratified as ED (+) or ED (-) based on a cut-off value of 6.5%. The PE patients were divided as early/late onset PE and severe/mild PE. Adropin, ATX, and LPA levels were measured, and their relevance to ED was evaluated. Student t, Mann-Whitney U, or ANOVA tests were used for statistics, as appropriate. Adropin levels were diminished in the ED (+) group, whereas ATX and LPA levels were increased. The decrease in adropin levels was more pronounced in severe PE, showing a positive correlation with the FMD. In the logistic regression model, adropin was the only parameter that was an independent variable for the FMD test (P < .001). Adropin measurements in serum may be of value for disease follow-up in patients with PE., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy., Methods: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months. Plasma cytokines, blood pressure, microvessel density, and vascular reactivity were assessed., Results: 6-month-old infants born to mothers with Pre-E had unchanged blood pressure (p = 0.86) and microvessel density (p = 0.57). Vascular reactivity was decreased in infants born to mothers with Pre-E compared to infants born to healthy mothers (p = 0.0345). Interleukin 8 (IL-8) (p = 0.03) and Angiopoeitin-2 (Ang-2) (p = 0.04) were increased in infants born to mothers with Pre-E. We observed that higher IL-8 was associated with lower vascular reactivity (rho = -0.14, p < 0.0001)., Conclusion: At 6 months of age, infants born to mothers with Pre-E had impaired vascular reactivity and higher IL-8 and Ang-2, but similar blood pressure and microvessel density compared to infants born to non-Pre-E mothers., Impact Statement: Changes in cord blood antiangiogenic factors are documented in infants of mothers with pre-eclampsia and may contribute to offspring risks of adult cardiovascular disease. How these factors evolve during early infancy and their correlation with offspring vascular development have not been studied. This study found that 6-month-old infants born to mothers with pre-eclampsia had decreased vascular reactivity, which was correlated with higher IL-8. These findings underscore the lasting impact of maternal pre-eclampsia on offspring vascular development and highlight the need for long-term follow-up in children born to mothers with pre-eclampsia., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models., Methods: Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling., Results: CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction., Conclusions: Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia., Competing Interests: None.

Objectives: Magnesium sulfate (MgSO 4 ) is one of the most commonly used agents for the treatment and prophylaxis of eclampsia in patients with severe preeclampsia. However, there is no international consensus regarding the optimal gestational age for MgSO4 treatment. The aim of this study was to assess the effect of MgSO4 on uterine (UtA), umbilical, and fetal middle cerebral arteries (MCA) by calculating the SD ratio (S/D), resistance index (RI), and pulsatility index (PI) at different gestational weeks., Methods: In total, 66 pregnant women as participants with severe preeclampsia were divided into two groups based on gestational age: Group 1 ( n  = 28, 26-30 weeks) and Group 2 ( n  = 38, 30-34 weeks). Color Doppler (Philip HD11) measurements were taken and compared before and after the MgSO4 loading dose., Results: Within-group analysis revealed significant differences in RI-UtA, PI-UtA, and S/D in UtA before and after MgSO4 administration in Group 1. Furthermore, the RI-UA and RI-MCA decreased statistically significantly after MgSO4 treatment, whereas the pulsatility index and S/D did not change in either the umbilical or middle cerebral arteries. After MgSO4 treatment, all Doppler parameters in the uterine and umbilical arteries in Group 2 showed significant changes when compared to before MgSO4 administration., Conclusion: MgSO4 can effectively improve umbilical and MCA blood flow at 30-34 gestational weeks but not at 26-30w. Meanwhile, using MgSO4 can improve uterine blood flow in severe preeclampsia, which may contribute to the management of reducing adverse events in pregnant women who have preeclampsia and fetal growth restriction.

Objective: To investigate the influence of different measurement conditions and ultrasound training level on uterine artery pulsatility index (UtA-PI) measurements as required for combined first trimester preeclampsia (PE) screening., Methods: This was a prospective study of consecutive patients with singleton pregnancies presenting for an ultrasound examination between 11 and 14 weeks' gestation. UtA-PI measurements were conducted by residents in training and repeated by experienced sonographers thereafter. UtA-PI measurements were conducted under different examination conditions. First, the trainee sonographers performed transabdominal sagittal and transverse UtA-PI measurements without bladder filling. These measurements were then repeated by the expert sonographers. Additionally, the expert sonographers also performed transvaginal UtA-PI measurements and transabdominal measurements with bladder filling. Statistical analysis was conducted with the statistical software R and included descriptive statistics as well as 2-sided paired t tests., Results: A total of 100 women were included in the study. Mean age was 31.7 ± 4.92 years and mean gestational week was 12.5 ± 0.53 weeks. A total of 56% were nulliparous and 44% were parous. UtA-PI was significantly lower if performed by a sonographer in training versus an experienced sonographer (P = .031). No significant difference was observed in comparing transverse and sagittal techniques (P = .241). There was also no significant difference in transabominal versus transvaginal measurements (P = .806) and with an empty versus full bladder (P = .444)., Conclusion: Experience of sonographer has a significant impact on UtA-PI. Supervised onsite training is necessary to improve reliability and consistency of UtA-PI measurements and make PE screening reliable for implementation in a universal screening setting., (© 2024 The Author(s). Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia.   Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Purpose of Review: For a healthy pregnancy to occur, a controlled interplay between the maternal circulating renin-angiotensin-aldosterone system (RAAS), placental renin-angiotensin system (RAS) and intrarenal renin-angiotensin system (iRAS) is necessary. Functionally, both the RAAS and iRAS interact to maintain blood pressure and cardiac output, as well as fluid and electrolyte balance. The placental RAS is important for placental development while also influencing the maternal circulating RAAS and iRAS. This narrative review concentrates on the (pro)renin receptor ((P)RR) and its soluble form (s(P)RR) in the context of the hypertensive pregnancy pathology, preeclampsia., Recent Findings: The (P)RR and the s(P)RR have become of particular interest as not only can they activate prorenin and renin, thus influencing levels of angiotensin II (Ang II), but s(P)RR has now been shown to directly interact with and stimulate the Angiotensin II type 1 receptor (AT 1 R). Levels of both placental (P)RR and maternal circulating s(P)RR are elevated in patients with preeclampsia. Furthermore, s(P)RR has been shown to increase blood pressure in non-pregnant and pregnant rats and mice. In preeclamptic pregnancies, which are characterised by maternal hypertension and impaired placental development and function, we propose that there is enhanced secretion of s(P)RR from the placenta into the maternal circulation. Due to its ability to both activate prorenin and act as an AT 1 R agonist, excess maternal circulating s(P)RR can act on both the maternal vasculature, and the kidney, leading to RAS over-activation. This results in dysregulation of the maternal circulating RAAS and overactivation of the iRAS, contributing to maternal hypertension, renal damage, and secondary changes to neurohumoral regulation of fluid and electrolyte balance, ultimately contributing to the pathophysiology of preeclampsia., (© 2024. The Author(s).)

Background: Prediabetes (PD) is associated with intermediate hyperglycaemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE., Methods: Pregnant female Sprague-Dawley rats ( N  = 18) were divided into normal, preeclamptic and prediabetic groups ( n  = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey-Kramer post hoc test. Values of p  < .05 were used to indicate statistical significance., Results: Maternal PD and PE significantly increased blood glucose, decrease NO concentration and increase in MAP by comparison to the normal pregnant control group. Maternal PD significantly decreased VEGF, PlGF mRNA expression with a slight increase in sFlt-1 mRNA expression comparison to the normal pregnant control group., Conclusions: Maternal PD is associated with placental dysfunction due to impaired glucose handling, endothelial dysfunction and an imbalance in angiogenic and antiangiogenic factors. Therefore, maternal PD is a risk factor of PE.

Objective: To analyze the changes in cardiac structure and function in women with different types of hypertensive disorders in pregnancy (HDP) and explore their influencing factors. Methods: A total of 1 967 pregnant women diagnosed with HDP who delivered at Peking University Third Hospital from January 1, 2014 to April 15, 2022 were included in the study. They were categorized into four groups based on specific HDP diagnoses: gestational hypertension (506 cases, 25.7%), pre-eclampsia (589 cases, 29.9%), pregnancy complicated with chronic hypertension (332 cases, 16.9%) and chronic hypertension with pre-eclampsia (540 cases, 27.5%). Differences in cardiac structure and function among four groups were retrospectively analyzed. Cardiac structure indicators included left atrial diameter (LAD), left atrial area (LAA), right atrial area (RAA), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), systolic function indicators included left ventricular ejection fraction (LVEF), lateral systolic mitral annular velocity (Sm), diastolic function indicators included peak early diastolic mitral in flow velocity (E)/peak late diastolic mitral in flow velocity (A), and E/peak early diastolic myocardial velocity of the lateral mitral annulus early diastolic velocity (Em). Influencing factors on cardiac structure and function were analyzed using generalized linear regression. Influencing factors were assessed by generalized linear regression. Results: (1) General clinical data: the differences in age, gestational week at delivery, blood pressure, proportion of diabetes, and length of hospital stay were statistically significant among four different HDP types (all P <0.05). (2) Compared with pregnant women with pregnancy complicated with chronic hypertension, pre-eclampsia, and gestational hypertension, those with chronic hypertension with pre-eclampsia had larger LAD, LAA, RAA and LVEDD (all P <0.001), thicker IVST and LVPWT (all P <0.001), and reduced left ventricular diastolic function (E/A, lateral Em, E/Em) and systolic function (lateral Sm; all P <0.001). Pregnant women with gestational hypertension had the least changes in cardiac structure and function. Compared with pregnant women with pre-eclampsia, those with pregnancy complicated with chronic hypertension had smaller RAA ( P <0.001) and lower E/A ( P <0.001), with no significant difference in other indicators (all P >0.05). (3) Chronic hypertension with pre-eclampsia, pregnancy complicated with chronic hypertension, and pre-eclampsia were associated with larger LAD, LAA, and LVEDD, and lower lateral Em (all P <0.05). Conclusions: Different types of HDP are associated with distinct changes in cardiac structure and function. Chronic hypertension with pre-eclampsia demonstrates the most pronounced alterations, followed by pre-eclampsia and pregnancy complicated with chronic hypertension, and gestational hypertension showed the least changes.

After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE., (© 2024. The Author(s).)

Background: We evaluated how elevated blood pressure in children exposed to preeclampsia (PE) impacted on their cardiac structure and function, as well as relations with maternal, gestational, and perinatal factors and child body size and composition., Methods and Results: A total of 182 PE (46 early-onset preeclampsia) and 85 unexposed (non-PE) children were examined in the FINNCARE study 8 to 12 years after the index pregnancy with echocardiography; office, central, and 24-hour ambulatory blood pressures; and body anthropometrics and composition. PE children had lower right ventricular basal sphericity index (mean difference, -0.26 95% CI, -0.39 to -0.12) and lower mitral lateral E '-wave peak velocity (-1.4 cm/s [95% CI, -2.1 to -0.6]), as well as higher E to E ' ratio (0.40 [95% CI, 0.15-0.65]) and indexed tricuspid annular plane systolic excursion (0.03 [95% CI, 0.01-0.05]) compared with non-PE children. These differences were accentuated in early-onset PE children. Left ventricular mass (LVM) or left atrial volume were not different between PE and non-PE children. Lean body mass, body fat percentage, and 24-hour systolic blood pressure were independent predictors of LVM. Lean body mass and body fat percentage were independent predictors of left atrial volume. No significant associations between LVM or left atrial volume and maternal, gestational, or perinatal parameters were found., Conclusions: Preadolescent PE children display a more globular-shaped right ventricle with higher longitudinal systolic displacement as well as mildly altered diastolic indices, with the alterations being pronounced in early-onset preeclampsia. Lean body mass and adiposity are independently related with LVM and left atrial volume, and systolic blood pressure with LVM in both PE and non-PE children. These unfavorable associations indicate remodeling of cardiac structure in young children also reflected in mild functional changes in PE children., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT04676295.

Does our time inside the womb predict our future? Evidence suggests that the environment in the womb plays a powerful role in predicting specific adult diseases. The fetus is constantly responding and adapting to the intrauterine environment by a process called programming. Toxic exposures, such as nutritional deficits and hypoxia, can affect fetal development and increase the risk for specific diseases that manifest later in our adult life. Preeclampsia (PE) is one disorder that results in a less-than-optimal environment for the growing fetus. It is pregnancy-specific and defined as new-onset hypertension after 20 weeks' gestation in the presence of maternal multiorgan dysfunction. To the best of our understanding, the pathogenesis is multifactorial and involves dysfunction of the placenta and the vascular, renal, and immunological systems. Treatment options are limited and may result in adverse outcomes for the fetus and newborn. Preeclampsia is a major contributor to perinatal and maternal morbidity and mortality worldwide, thus generating a significant healthcare burden. Research continues to demonstrate that mothers and infants affected by PE are at increased susceptibility to chronic conditions such as cardiovascular, renal, metabolic, and neurological diseases. More efforts are needed to further understand this disease. Efforts to increase awareness will help improve clinical outcomes for both mothers and infants., (© 2024 Springer Publishing Company, LLC.)

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: New-onset proteinuria, as a pivotal sign of representative renal lesions in preeclampsia, is still the most common diagnostic tool for this condition and has been proven to be related to a significantly abnormal sFlt-1/VEGF ratio in circulation. At the same time, blood pressure control plays a vital role in the occurrence and evolution of proteinuria. Therefore, it is particularly helpful to investigate their interval, not only for performing urinalysis for protein more accurately but also for evaluating blood pressure as well as the aggravation of illness, as the related research is limited., Methods: This retrospective study included 515 preeclampsia patients and 358 normotensive pregnant women who labored in the Second Hospital of Tianjin Medical University from January 2016 to January 2020. First, we described the onset circumstance of high blood pressure and proteinuria as well as the interval among the case group and the subgroups. Then, we determined whether there were significant differences in the basic information, laboratory test results, and newborns between the case and normal groups. Finally, multifactor ANOVA was used to determine the factors influencing the interval., Results: 1. The two most common complications in preeclampsia were proteinuria (88.35%) and placental dysfunction (5.05%). Moreover, 72.04% of preeclampsia cases were diagnosed by abnormal blood pressure together with new-onset proteinuria. 2. The average interval between high blood pressure and proteinuria was 22 gestational days (from 0 to 106 days), and this interval was not significantly different between mild and severe PE (26 days vs. 21 days, P > 0.05) but significantly differed between early-onset and late-onset PE (9 days vs. 28 days, P < 0.05). 3. The number of prenatal visits, serum creatinine in the early trimester, gestational time and diastolic blood pressure value when increased blood pressure was initially detected may influence the interval between the onset of increased blood pressure and proteinuria., Conclusion: New-onset proteinuria was still the main parameter for identifying preeclampsia. The interval between increased blood pressure and proteinuria was probably related to the imbalance in the sFlt-1/VEGF ratio; therefore, we should pay attention to monitor proteinuria during the prenatal visits, especially for patients with a lower frequency of prenatal visits, higher serum creatinine in the early trimester, earlier onset and higher diastolic blood pressure at the initial onset of increased blood pressure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: After a hypertensive disorder of pregnancy, hypertension can worsen in the postpartum period following hospital discharge. Risk factors for ongoing hypertension and associated outcomes have not been well characterized., Objective: To identify risk factors and characterize outcomes for individuals with ongoing hypertension and severe hypertension following hospital discharge post partum through a hospital system's remote blood pressure (BP) management program., Design, Setting, and Participants: This cohort study involved a population-based sample of individuals with a new-onset hypertensive disorder of pregnancy (preeclampsia or gestational hypertension) and no prepregnancy hypertension who delivered between September 2019 and June 2021. Participants were enrolled in a remote BP monitoring and management program at a postpartum unit at a referral hospital. Data analysis was performed from August 2021 to January 2023., Exposure: Inpatient postpartum BP categories., Main Outcomes and Measures: The primary outcomes were readmission and emergency department visits within the first 6 weeks post partum. Logistic regression was used to model adjusted odds ratios (aORs) and 95% CIs., Results: Of 2705 individuals in the cohort (mean [SD] age, 29.8 [5.7] years), 2214 (81.8%) had persistent hypertension post partum after hospital discharge, 382 (14.1%) developed severe hypertension after discharge, and 610 (22.6%) had antihypertensive medication initiated after discharge. Individuals with severe hypertension had increased odds of postpartum emergency department visits (aOR, 1.85; 95% CI, 1.17-2.92) and hospital readmissions (aOR, 6.75; 95% CI, 3.43-13.29) compared with individuals with BP normalization. When inpatient postpartum BP categories were compared with outpatient home BP trajectories to inform optimal thresholds for inpatient antihypertensive medication initiation, there was significant overlap between postdischarge BP trajectories among those with inpatient systolic BP greater than or equal to 140 to 149 mm Hg and/or diastolic BP greater than or equal to 90 to 99 mm Hg and those with systolic BP greater than or equal to 150 mm Hg and/or diastolic BP greater than or equal to 100 mm Hg., Conclusions and Relevance: This cohort study found that more than 80% of individuals with hypertensive disorders of pregnancy had ongoing hypertension after hospital discharge, with approximately 14% developing severe hypertension. These data support the critical role of remote BP monitoring programs and highlight the need for improved tools for risk stratification and consideration of liberalization of thresholds for medication initiation post partum.