Normotensive Pregnancies Research Articles

Functional connectivity of limbic system and prefrontal cortex years after pre-eclampsia: 7-Tesla functional magnetic resonance imaging study.

Pre-eclampsia is a vascular complication of pregnancy, associated with a long-term risk of cerebrovascular and mental disorders. We explored whether formerly pre-eclamptic women exhibit differences in functional brain organization, especially in regions that may explain the commonly reported emotional symptoms and cognitive complaints even years after the pregnancy. Formerly pre-eclamptic women and control women with a history of normotensive pregnancy underwent structural and functional 7-Tesla magnetic resonance imaging scans. Using graph theoretical analysis, the efficiency and clustering coefficient of the functional brain network were investigated. The study included local analysis focusing on particular brain structures, such as the limbic system and the prefrontal cortex, and global analysis of the whole cerebrum. Univariable and multivariable linear regression was used to investigate the relationship between brain network-related graph measures and the group (formerly pre-eclamptic or control). A total of 17 control parous women and 55 women with a history of pre-eclampsia were recruited. The time intervals between the index pregnancy and recruitment were 8.0 and 5.6 years for the two groups, respectively. Compared with control women, formerly pre-eclamptic women had higher local efficiency in the prefrontal cortex (P = 0.048) and anterior cingulate cortex (P = 0.03) but lower local efficiency and local clustering coefficient in the amygdala (P = 0.004 and P = 0.02, respectively) and parahippocampal cortex (P = 0.007 and P = 0.008, respectively). No differences were found in the global functional brain organization. Compared to controls with a history of normotensive pregnancy, formerly pre-eclamptic women displayed a different local functional brain organization. These differences in functional connectivity, especially in the limbic regions and the prefrontal cortex, are in line with the psychological and cognitive complaints reported commonly by women with a history of pre-eclampsia. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Blood-brain barrier leakage years after pre-eclampsia: dynamic contrast-enhanced 7-Tesla MRI study.

Pre-eclampsia is a hypertensive complication of pregnancy that is associated with an increased risk of long-term cardiovascular and cerebrovascular disorders. Although the underlying mechanism of persistent susceptibility to cerebral complications after pre-eclampsia remains largely unclear, impaired blood-brain barrier (BBB) integrity has been suggested to precede several cerebrovascular diseases. In this study, we aimed to investigate the integrity of the BBB years after pre-eclampsia. This was an observational study of premenopausal formerly pre-eclamptic women and controls with a history of normotensive pregnancy who underwent cerebral magnetic resonance imaging (MRI) at ultra-high field (7Tesla) to assess the integrity of the BBB. Permeability of the BBB was determined by assessing leakage rate and fractional leakage volume of the contrast agent gadobutrol using dynamic contrast-enhanced MRI. BBB leakage measures were determined for the whole brain and lobar white and gray matter. Multivariable analyses were performed, and odds ratios were calculated to compare women with and those without a history of pre-eclampsia, adjusting for potential confounding effects of age, hypertension status at MRI and Fazekas score. Twenty-two formerly pre-eclamptic women (mean age, 37.8 ± 5.4 years) and 13 control women with a history of normotensive pregnancy (mean age, 40.8 ± 5.5 years) were included in the study. The time since the index pregnancy was 6.6 ± 3.2 years in the pre-eclamptic group and 9.0 ± 3.7 years in controls. The leakage rate and fractional leakage volume were significantly higher in formerly pre-eclamptic women than in controls in the global white (P = 0.001) and gray (P = 0.02) matter. Regionally, the frontal (P = 0.04) and parietal (P = 0.009) cortical gray matter, and the frontal (P = 0.001), temporal (P < 0.05) and occipital (P = 0.007) white matter showed higher leakage rates in formerly pre-eclamptic women. The odds of a high leakage rate after pre-eclampsia were generally higher in white-matter regions than in gray-matter regions. This observational study demonstrates global impairment of the BBB years after a pre-eclamptic pregnancy, which could be an early marker of long-term cerebrovascular disorders. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Decidual dendritic cells 10 and CD4+CD25+FOXP3 regulatory T cell in preeclampsia and their correlation with nutritional factors in pathomechanism of immune rejection in pregnancy

BackgroundImmune intolerance is thought to be the underlying cause of immune rejection to fetus in preeclampsia. Decidual dendritic cell-10 (DC-10) and T regulator cell (Treg) play important role to create tolerogenic environment during pregnancy. However, their roles on the specific pathomechanism of preeclampsia along with various nutritional factors have not been widely studied. AimTo determine the number of DC-10 and Treg in preeclampsia and their correlations with decidual nutritional factors. MethodThis was a cross-sectional study among early onset preeclampsia (EOPE), late onset preeclampsia (LOPE), and normotensive (NT) pregnancies. Decidual specimens were obtained by curettage after caesarean section. The number of DC-10 and Treg cells were counted using flow cytometry. The levels of nutritional factors (zinc, retinol, all-trans retinoic acid, vitamin D) were determined using ICP-MS and LC-MS method. ResultA total of 14 subjects for each group were included in the study. The DC-10 was significantly lower in both EOPE and LOPE compared to NT (p < 0.001). Treg cells were significantly higher in EOPE compare to NT (p = 0.015). There was a moderate correlation between zinc level and DC-10 (p = 0.011) and a strong correlation between retinol level and DC-10 (p = 0.002) in the NT group. A moderate correlation was found between vitamin D level and Treg cells in the NT group (p = 0.026). ConclusionThere was a lower number of DC-10 and higher number of Treg cells in early preeclampsia. There was no correlation between DC-10 and Treg number with decidual nutritional factors in preeclampsia.

Coronary Artery Restenosis in Women by History of Preeclampsia.

Background A history of preeclampsia is associated with increased risk of coronary artery disease and experimental evidence suggests that a history of preeclampsia also increases the risk of restenosis. However, the extent to which a history of preeclampsia is associated with risk of restenosis after percutaneous coronary intervention in women is unknown. Methods and Results We included 6065 parous women aged ≤65 years with first percutaneous coronary intervention on 9452 segments 2006 to 2017, linking nationwide data on percutaneous coronary intervention and delivery history in Sweden. Main outcomes were clinical restenosis and target lesion revascularization within 2 years. We accounted for segment-, procedure-, and patient-related potential predictors of restenosis in proportional hazards regression models. Restenosis occurred in 345 segments (3.7%) and target lesion revascularization was performed on 383 patients (6.3%). A history of preeclampsia was neither significantly associated with risk of restenosis (predictor-accounted hazard ratio [HR], 0.71 [95% CI, 0.41-1.23]) nor target lesion revascularization (0.74 [95% CI, 0.51-1.07]) compared with a normotensive pregnancy history. When term and preterm preeclampsia were investigated separately, segments in women with a history of term preeclampsia had a lower risk of restenosis (predictor-accounted HR, 0.45 [95% CI, 0.21-0.94]). A history of preeclampsia was not significantly associated with death by any cause within 2 years of the index procedure (predictor-accounted HR 1.06, [95% CI, 0.62-1.80]). Conclusions A history of preeclampsia was not associated with increased risk of restenosis but instead some evidence pointed to a decreased risk. To facilitate future studies and allow for replication, concomitant collection of data on pregnancy complication history and percutaneous coronary intervention outcomes in women is warranted.

Abstract P102: A History Of Preeclampsia Is Associated With Accelerated Aging And Multimorbidity Later In Life

Background: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder which affects up to 7% of all pregnancies. It is associated with increased risk for cardiovascular disease later in life. We have recently reported increased senescence and accelerated aging in women with PE. We hypothesize that senescence burden remains after PE. The aim of this study was to compare senescence profiles, and history of individual chronic conditions and multimorbidity, a marker of accelerated aging, in women with and without a history of PE. Methods: Forty women with histories of PE and 40 with histories of normotensive pregnancy confirmed by manual chart review were age- and parity-matched. None of the women had a history of CVD at the time of recruitment. Markers of senescence (p16, p21 and Klotho) and metabolic syndrome (leptin, adiponectin) were measured and compared between women with and without histories of preeclampsia using conditional logistic regression. The rates of chronic conditions and multimorbidity between the groups were also compared. Results: Urinary Klotho/creatinine levels were significantly lower (median [IQR]: 117 [87.4, 224] vs. 205 [101, 359], respectively, p=0.042), while leptin/adiponectin ratio was significantly higher (median [IQR]: 0.25 [0.13, 0.45] vs. 0.05 [0.02, 0.12], p=0.027) among women with histories of PE compared to controls. There were no significant differences observed in plasma p21 or p16 concentrations. Women with histories of PE experienced a higher prevalence of two or more co-morbidities compared to women with normotensive pregnancies [67.5% (27/40) vs. 22.5% (9/40), p&lt;0.05]. Results were similar after removing hypertension as a comorbidity [45% (18/40) vs. 20.0% (8/40), p&lt;0.05]. Conclusion: Women with a history of PE had altered markers of senescence, metabolic syndrome and multimorbidity decades after PE.

Integrative exposomic, transcriptomic, epigenomic analyses of human placental samples links understudied chemicals to preeclampsia.

Environmental health research has recently undergone a dramatic shift, with ongoing technological advancements allowing for broader coverage of exposure and molecular biology signatures. Approaches to integrate such measures are still needed to increase understanding between systems-level exposure and biology. We address this gap by evaluating placental tissues to identify novel chemical-biological interactions associated with preeclampsia. This study tests the hypothesis that understudied chemicals are present in the human placenta and associated with preeclampsia-relevant disruptions, including overall case status (preeclamptic vs. normotensive patients) and underlying transcriptomic/epigenomic signatures. A non-targeted analysis based on high-resolution mass spectrometry was used to analyze placental tissues from a cohort of 35 patients with preeclampsia (n = 18) and normotensive (n = 17) pregnancies. Molecular feature data were prioritized for confirmation based on association with preeclampsia case status and confidence of chemical identification. All molecular features were evaluated for relationships to mRNA, microRNA, and CpG methylation (i.e., multi-omic) signature alterations involved in preeclampsia. A total of 183 molecular features were identified with significantly differentiated abundance in placental extracts of preeclamptic patients; these features clustered into distinct chemical groupings using unsupervised methods. Of these features, 53 were identified (mapping to 40 distinct chemicals) using chemical standards, fragmentation spectra, and chemical metadata. In general, human metabolites had the largest feature intensities and strongest associations with preeclampsia-relevant multi-omic changes. Exogenous drugs were second most abundant and had fewer associations with multi-omic changes. Other exogenous chemicals (non-drugs) were least abundant and had the fewest associations with multi-omic changes. These global data trends suggest that human metabolites are heavily intertwined with biological processes involved in preeclampsia etiology, while exogenous chemicals may still impact select transcriptomic/epigenomic processes. This study serves as a demonstration of merging systems exposures with systems biology to better understand chemical-disease relationships.

Competing-risks model for pre-eclampsia and adverse pregnancy outcomes.

The competing-risks model for assessment of risk for pre-eclampsia (PE) at 35-37 weeks' gestation identifies the majority of women who are at high risk of subsequent delivery with PE. We aimed to examine the incidence and relative risk of adverse pregnancy outcomes in patient groups stratified according to the estimated risk of delivery with PE. This was a prospective non-interventional, observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The risk of delivery with PE for each patient in the study population was estimated using the competing-risks model, combining the prior distribution of gestational age at delivery with PE and the likelihood from multiples of the median values of mean arterial pressure, placental growth factor and soluble fms-like tyrosine kinase-1. The patients were assigned to one of the following five risk categories: Group A, ≥ 1 in 2; Group B, 1 in 5 to 1 in 3; Group C, 1 in 20 to 1 in 6; Group D, 1 in 50 to 1 in 21; and Group E, < 1 in 50. The outcome measures were delivery with PE, gestational hypertension (GH), small-for-gestational age (SGA) at birth, delivery by Cesarean section, stillbirth, neonatal death, perinatal death and admission to the neonatal unit (NNU) for at least 48 h. In each risk category, the proportion of women with each adverse outcome was determined and relative risks (RR) were calculated as compared with the lowest-risk Group E. In the study population of 29 035 women, 1.6%, 2.7%, 8.2%, 9.8% and 77.8% were categorized into Groups A, B, C, D and E, respectively. Compared with women in Group E, women in the higher-risk groups were more likely to have an adverse outcome. The RR of delivery with PE in Group A compared with Group E was 65.5 (95% CI, 54.1-79.1) and the respective values were 11.9 (95% CI, 9.1-15.5) for GH, 1.8 (95% CI, 1.5-2.1) for delivery by emergency Cesarean section, 1.5 (95% CI, 1.2-1.8) for delivery by elective Cesarean section, 8.9 (95% CI, 7.4-10.8) for SGA with birth weight < 3rd percentile, 4.8 (95% CI, 4.3-5.4) for SGA with birth weight < 10th percentile, 5.3 (95% CI, 1.4-20.5) for stillbirth and 3.4 (95% CI, 2.8-4.2) for NNU admission for ≥ 48 h. The RR for these pregnancy complications in higher-risk groups (vs Group E) was particularly high for cases with delivery within 2 weeks after assessment. In terms of SGA, both for birth weight < 10th and < 3rd percentiles, the trend in all cases was stronger than that observed when the analysis was confined to normotensive pregnancies. The rates of neonatal death were too small to allow meaningful comparisons between risk groups. Pregnant women identified by the competing-risks model to be at high risk of PE are also at increased risk of GH, Cesarean section, stillbirth, SGA and NNU admission for ≥ 48 h. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Soluble urinary somatic angiotensin converting enzyme is overexpressed in patients with preeclampsia: a potential new marker for the disease?

ABSTRACT Objective The aim of this study was to identify and quantify urinary Angiotensin-Converting-Enzyme (ACE) in hypertensive disorders of pregnancy. Methods Urine samples were analyzed by Western blot. Patients were classified into: normotensive pregnancy (N); preeclampsia and superimposed preeclampsia (PE+SPE); and gestational hypertension (GH). Results Somatic ACE protein expression was higher in PE+SPE compared to N and GH. There was a positive correlation between ACE and urinary protein to creatinine ratio, systolic and diastolic blood pressures. Conclusion These results indicate ACE overexpression in the urine of preeclamptic patients and suggest that it may be a new marker for the disease.

Association of Corpus Callosum Development With Fetal Growth Restriction and Maternal Preeclampsia or Gestational Hypertension

It remains unknown whether neurodevelopmental impairments are directly associated with the structural development of the brain in offspring with fetal growth restriction (FGR) and mothers with preeclampsia (PE) or gestational hypertension (GH). To assess whether fetal corpus callosum (CC) development differed among pregnancies with PE or GH with FGR, pregnancies with PE or GH without FGR, and normotensive pregnancies, particularly the severity of maternal disease and FGR, and to identify the association between adverse perinatal outcomes and structural development of the CC in fetuses with FGR in pregnancies with PE or GH. This retrospective matched case-control study was conducted between January 1, 2014, and January 31, 2021, at Women's Hospital, Zhejiang University School of Medicine in Hangzhou, China. The participant group included cases of singleton pregnancies with PE or GH with FGR; the control groups included cases with PG or GH without FGR and cases with paired normotensive pregnancy. Maternal PE or GH and FGR. The length, thickness, total area, subdivision areas, and apparent diffusion coefficient (ADC) values of fetal CC were measured on magnetic resonance imaging (MRI) and analyzed. The association between adverse perinatal outcomes and structural development of CC was further investigated. A total of 56 pregnant individuals with singleton pregnancies and PE or GH and fetuses with FGR were enrolled (maternal median [IQR] age, 29.0 [26.0-34.0] years; mean [SD] gestational age at MRI, 33.6 [2.5] weeks). Significant patterns of decreased median (IQR) fetal CC length (0.4284 [0.4079-0.4470] mm vs 0.4614 [0.4461-0.4944] mm, P < .001, vs 0.4591 [0.4310-0.4927] mm, P < .001) and mean (SD) CC total area (1.0779 [0.1931] mm2 vs 1.1896 [0.1803] mm2, P = .001, vs 1.1438 [0.1935] mm2, P = .02), adjusted for the cephalic index, was observed in cases of PE or GH with FGR compared with cases without FGR and cases with normotensive pregnancy. The splenium region of fetal CC also exhibited the distinct alterations in macrostructural development (with FGR: 0.3149 [0.0697] mm2 vs without FGR: 0.3727 [0.0698] mm2, P < .001, vs normotensive pregnancies: 0.3565 [0.0763] mm2, P < .001) and microstructural development (median [IQR] ADC values: 1.47 [1.38-1.57] × 10-3 mm2/s vs 1.57 [1.53-1.63] × 10-3 mm2/s, P = .009, vs 1.63 [1.50-1.70] × 10-3 mm2/s, P < .001) in all groups. Furthermore, significant associations were found between structural abnormality of the splenium region and adverse perinatal outcomes in the PE or GH with FGR group (mean [SD] ADC value: 1.40 [0.07] × 10-3 mm2/s; P = .04). Results of this study suggest that, in fetuses with FGR in pregnancies with PE or GH, decreased structural development of the CC, predominantly the splenium region, may be significantly associated with a higher risk of adverse perinatal outcomes and may be regarded as an MRI-based biomarker for better prenatal counseling and early management decisions.

Early-onset preeclampsia is characterised by an increased vascular tone in internal jugular veins.

PurposeThis study aimed to investigate Doppler characteristics of maternal internal jugular veins in uncomplicated pregnancies vs. those affected by hypertensive disorders.Materials and methodsVenous pulse transit time and venous impedance index were measured at three different locations (right proximal, right distal, left proximal) of internal jugular veins according to a standardised combined Doppler-Electrocardiogram protocol in five different groups of pregnant women: uncomplicated pregnancy, early-onset preeclampsia, late-onset preeclampsia, gestational hypertension, and normotensive pregnancies with a small for gestational age foetus. Values of both parameters of the latter four groups were plotted against the reference range of uncomplicated pregnancies at corresponding gestation. Linear mixed models with random intercept were used to investigate gestational changes in venous pulse transit time and venous impedance index at the three internal jugular vein locations within and between the different groups.ResultsA total of 127 women were included: 41 had uncomplicated pregnancies, 13 had early-onset preeclampsia, 25 had late-onset preeclampsia, 22 had gestational hypertension, and 26 had normotensive pregnancies with a small for gestational age foetus. Venous pulse transit time values were lower than uncomplicated pregnancy (p ≤ 0.001) at all three locations in the third trimester of early-onset preeclampsia.ConclusionContrary to late-onset preeclampsia and gestational hypertension, early-onset preeclampsia is characterised by a lower venous pulse transit time at internal jugular veins compared to uncomplicated pregnancy, suggesting increased venous vascular tone.

Characterization of the MG828507 lncRNA Located Upstream of the FLT1 Gene as an Etiology for Pre-Eclampsia.

Background: FLT1 is one of the significantly overexpressed genes found in a pre-eclamptic placenta and is involved with the etiology of this disease. Methods: We conducted genome-wide expression profiling by RNA-seq of placentas from women with pre-eclampsia and those with normotensive pregnancy. Results: We identified a lncRNA gene, MG828507, located ~80 kb upstream of the FLT1 gene in a head-to-head orientation, which was overexpressed in the pre-eclamptic placenta. MG828507 and FLT1 are located within the same topologically associated domain in the genome. The MG828507 mRNA level correlated with that of the FLT1 in placentas from pre-eclamptic women as well as in samples from uncomplicated pregnancies. However, neither the overexpression nor knockdown of MG828507 affected the expression of FLT1. Analysis of pre-eclampsia-linking genetic variants at this locus suggested that the placental genotype of one variant was associated with the expression of MG828507. The MG828507 transcript level was not found to be associated with maternal blood pressure, but showed a relationship with birth and placental weights, suggesting that this lncRNA might be one of the pivotal placental factors in pre-eclampsia. Conclusion: Further characterization of the MG828507 gene may elucidate the etiological roles of the MG828507 and FLT1 genes in pre-eclampsia in a genomic context.

The cardiac-fetal-placental unit: fetal umbilical vein flow rate is linked to the maternal cardiac profile in fetal growth restriction

The functional maternal-fetal hemodynamic unit includes fetal umbilical vein flow and maternal peripheral vascular resistance. This study investigated the relationships between maternal and fetal hemodynamics in a population with suspected fetal growth restriction. This was a prospective study of normotensive pregnancies referred to our outpatient clinic for a suspected fetal growth restriction. Maternal hemodynamics measurement was performed, using a noninvasive device (USCOM-1A) and a fetal ultrasound evaluation to assess fetal biometry and velocimetry Doppler parameters. Comparisons among groups were performed with 1-way analysis of variance with Student-Newman-Keuls correction for multiple comparisons and with Kruskal-Wallis test where appropriate. The Spearman rank coefficient was used to assess the correlation between maternal and fetal hemodynamics. Pregnancies were observed until delivery. A total of 182 normotensive pregnancies were included. After the evaluation, 54 fetuses were classified as growth restricted, 42 as small for gestational age, and 86 as adequate for gestational age. The fetus with fetal growth restriction had significantly lower umbilical vein diameter (P<.0001), umbilical vein velocity (P=.02), umbilical vein flow (P<.0001), and umbilical vein flow corrected for fetal weight (P<.01) than adequate-for-gestational-age and small-for-gestational-age fetuses. The maternal hemodynamic profile in fetal growth restriction was characterized by elevated systemic vascular resistance and reduced cardiac output. The umbilical vein diameter was positively correlated to maternal cardiac output (rs=0.261), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.338) and maternal potential energy-to-kinetic energy ratio (rs=-0267). The fetal umbilical vein time averaged max velocity was positively correlated to maternal cardiac output (rs=0.189) and maternal inotropy index (rs=0.162), whereas there was a negative correlation with maternal systemic vascular resistance (rs=-0.264) and maternal potential energy-to-kinetic energy ratio (rs=-0.171). The fetal umbilical vein flow and the flow corrected for estimated fetal weight were positively correlated with maternal cardiac output (rs=0.339 and rs=0.297) and maternal inotropy index (rs=0.217 and r=0.336), whereas there was a negative correlation between maternal systemic vascular resistance (rs=-0.461 and rs=-0.409) and maternal potential energy-to-kinetic energy ratio (rs=-0.336 and rs=-0.408). Maternal and fetal hemodynamic parameters were different in the 3 groups of fetuses: fetal growth restriction, small for gestational age, and adequate for gestational age. Maternal hemodynamic parameters were closely and continuously correlated with fetal hemodynamic features. In particular, a maternal hemodynamic profile with high systemic vascular resistance, low cardiac output, reduced inotropism, and hypodynamic circulation was correlated with a reduced umbilical vein flow and increased umbilical artery pulsatility index. The mother, placenta, and fetus should be considered as a single cardiac-fetal-placental unit. The correlations of systemic vascular resistance, cardiac output, and inotropy index with umbilical artery impedance indicate the key role of these 3 parameters in placental vascular tree development. The umbilical vein flow rate and, therefore, the placental perfusion seems to be influenced not only by these three parameters but also by the maternal cardiovascular kinetic energy.

Plasma drop and thin-film revealed distinguished molecular structure in pre-eclampsia: An investigation using synchrotron Fourier-transform infrared microspectroscopy

Pre-eclampsia (PE) is a serious pregnancy-related disorder and the leading cause of maternal and fetal mortality and morbidity worldwide. The etiology of PE is poorly understood and a definitive diagnosis is still lacking. Herein, we used synchrotron-FTIR microspectroscopy as a new analytical tool to investigate the molecular changes in the structure and intensity of lipids (spectral range 3050–2800 cm−1) and protein-carbonyl (spectral range 1855–1485 cm−1) components of the plasma and link them to the pathogenesis of the disease. In the lipid region, an increase in the CH2 and CH3 peaks intensity was noticed in PE group compared to normotensive pregnancy reflecting abnormalities in the lipid profile and a high level of LDL. Increased CH2/CH3 ratio and red shifts were observed in the lipid region in PE highlighting structural variations of lipids and transformation of conformation of lipid tails. In the protein-carbonyl region, a decrease in the amide I and II absorption signals in the plasma of PE compared to normotensive controls was evident, and a red shift was noticed in the amide I region reflecting conformational changes and rearrangement in the α-helix secondary structure of the protein. Moreover, malondialdehyde level and lipid carbonyl peak at 1743 cm−1 were higher and more intense in PE due to the oxidative stress condition in PE. Spectral analysis of plasma drop from PE revealed that lipid and protein components tend to concentrate more in the central region of the drop, and that the most intense wavenumber values for the lipid and amide I region in the plasma drop were very comparable to their analogous in plasma film. Taken together, the current work provides evidence of the promising role of synchrotron-FTIR microspectroscopy in providing a better understanding of the pathophysiology of PE.

Association of fetal sex with angiogenic factors in normotensive and hypertensive pregnancy states.

With the incorporation of angiogenic biomarkers into clinical practice, identification of potential modifiers of the angiogenic profile, including fetal sex, is essential. In this retrospective cohort analysis, patients with hypertensive disorders of pregnancy (HDP) and normotensive pregnancies were enrolled upon admission to Labor and Delivery. Blood samples for angiogenic factors were assessed using an automated platform. Clinical and demographic information was abstracted from each patient's medical records. Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) levels and their ratio in relation to fetal sex in patients with normotensive pregnancies compared to those with HDP were evaluated. A total of 617 patients were analyzed (299 normotensive, 113 gestational hypertensive, 71 chronic hypertensive, and 134 preeclamptic patients). There was no difference between the number of patients who had a male fetus among preeclampsia and normotensive parturients (56.0% vs 50.2%, p=0.26). Normotensive patients carrying a male fetus had significantly higher sFlt1 (pg/ml) (3168 [IQR: 2160-4945] vs 2678 [IQR: 1752-4271]; p=0.01) and sFlt1/PlGF ratios (18 [IQR: 7-44] vs 12 [IQR: 5-30]; p=0.01) in comparison to pregnant patients carrying a female fetus. This difference between fetal sexes was not observed in the angiogenic profile of patients with HDP. Our study of primarily Black, obese patients demonstrates that normotensive patients carrying a male fetus have a significantly higher sFlt1 and sFlt1/PlGF ratio as compared to those carrying a female fetus at term gestation. Fetal sex should be considered as a covariate when studying angiogenic factors in normotensive pregnant patients.

Risk of future cardiovascular diseases in different years postpartum after hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Objective:There are limited data on the optimal timing and frequency of postpartum follow-up visits after hypertensive disorders of pregnancy (HDP) for primary prevention and early detection of cardiovascular diseases (CVDs) in high-risk women. We aimed to evaluate the risk of cardiovascular outcomes later in life in women with prior HDP in different years postpartum and in preeclamptic women with severe features, or early onset of preeclampsia.Methods:We searched MEDLINE, Cochrane Library, Web of Science, and Scopus without language restriction for relevant articles published from inception to March 16, 2022. We included prospective and retrospective cohort studies assessing hypertension, ischemic heart disease, heart failure, venous thromboembolism, peripheral vascular disease, stroke, dementia, composite cardiovascular and/or cerebrovascular diseases, and mortality after 6 weeks postpartum, in women with prior HDP compared with controls. Two authors independently selected and appraised the studies. Article quality was independently assessed using the Newcastle-Ottawa Scale (NOS). Random-effect models were used for meta-analysis. Stratified analyses based on years postpartum, severity, and onset of preeclampsia were performed.Results:We included 59 studies for qualitative review, of which 56 were included in quantitative meta-analysis, involving 1,262,726 women with prior HDP and 14,711,054 controls. Women with prior HDP had increased risks of hypertension (relative risk [RR] 3.46, 95% confidence interval [CI]: 2.67–4.49), ischemic heart disease (RR 2.06, 95% CI: 1.38–3.08), and heart failure (RR 2.53, 95% CI: 1.28–5.00) later in life, compared with those with normotensive pregnancies. The risk of hypertension was highest during 5 years postpartum (RR 5.34, 95% CI: 2.74–10.39). Compared with normotensive pregnancies, the risk of future CVDs significantly increased in preeclamptic women.Discussion:A history of HDP is associated with approximately 2- to 4-fold increase in the risk of CVDs. Screening for CVDs and their risk factors in women with prior HDP since delivery, especially the first 5 years after delivery is suggested for early detection and appropriate management. Evidence on the risks of CVDs in preeclampsia with severe features and early onset of preeclampsia is limited due to having few studies and high heterogeneity.Funding:The Royal Golden Jubilee PhD Program–RGJ (PHD/0183/2561); Thailand Science Research and Innovation (TSRI) Research Career Development Grant–RSA (RSA6180009); Targeted Research Grants Program of the Faculty of Medicine, Prince of Songkla University, Thailand.Registration:CRD42020191550

No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy.

IntroductionPreeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s).MethodsData was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models.ResultsOf the 1,217 included women (age range 22–62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: −0.48%/10 years (95% CI:−0.65 to −0.30%/10 years), NGMD: −1.13%/10 years (−1.49 to −0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD.ConclusionIn young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted. Impact statement What is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

Prevalence of a History of Metabolic or Hypertensive Pregnancy Disorder in Patients With Myocardial Infarction and Non-obstructive Coronary Arteries: An Observational Cohort Study.

IntroductionMyocardial infarction with non-obstructive coronary arteries (MINOCA) predominantly affects younger females. Women with a history of gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM) are subjected to an elevated lifetime risk of cardiovascular disease. However, data on the potential association between these obstetric complications and MINOCA is lacking. Therefore, the current study aimed to provide insight in the prevalence of metabolic and hypertensive pregnancy disorders (MHPD) in MINOCA patients and their clinical characteristics.MethodsIn this observational cohort study conducted at the Zuyderland Medical Center and Maastricht University Medical Center in the Netherlands, patients were enrolled if they were identified as having MINOCA. Data on individual patient characteristics, laboratory results, electrocardiography as well as (non-)invasive imaging procedures were derived from the electronic health record system. Patients were asked to complete a questionnaire about prior MHPD including GDM, GH, and PE. Patients were grouped into those with MHPD and those with prior uncomplicated normotensive pregnancy (or pregnancies; NP).ResultsAfter excluding patients without 1-year follow-up (n = 53), 86 female MINOCA patients remained eligible for analysis. Of the total female population, 25 (29.1%) patients had MHPD, including GH (n = 19; 22.1%), PE (n = 4; 4.7%), and GDM (n = 7; 8.1%). The MHPD patients showed higher rates of chronic hypertension (84.0 vs. 55.7%; p = 0.013), hypercholesterolemia (64.0 vs. 34.4%; p = 0.012), a family history of CVD (84.0 vs. 45.9%; p = 0.001), gout or rheumatic arthritis (16.0 vs. 1.6%; p = 0.024), and were more often non-smokers (45.8 vs. 78.3%; p = 0.004), compared to the NP patients. Moreover, MHPD patients were more likely to use cardiovascular medications at baseline. A trend toward no specific cause found for the MINOCA event was observed in MHPD patients compared to the NP group (64.0 vs. 42.6%, p = 0.072).ConclusionA history of metabolic and hypertensive pregnancy disorders occurred in one-third of female MINOCA patients. In these patients, conventional cardiovascular risk factors were more prevalent compared to NP patients. In most MHPD patients, the specific cause for MINOCA remained unclear.

Coagulation profile and platelet parameters in pregnancy induced hypertension cases and normotensive pregnancies: A cross-sectional study

•PIH is a leading cause of maternal and perinatal morbidity and mortality worldwide.•Hypercoagulability is constantly associated with hypertensive disorders of pregnancy and particularly associated with pre-eclampsia.•The aims and objectives of this study were to compare the platelet parameters and coagulation profile in normotensive pregnant females along with gestational hypertension cases and pre-eclamptia patients.

Decidual mesenchymal stem/stromal cells from preeclamptic patients secrete endoglin, which at high levels inhibits endothelial cell attachment invitro

IntroductionIn preeclampsia (PE), inadequate remodelling of spiral arterioles in the decidua basalis causes oxidative stress and subsequent increased release of antiangiogenic soluble endoglin (sENG) into the maternal circulation. Decidual mesenchymal stem/stromal cells (DMSCs) reside adjacent to endothelial cells in this vascular niche. Surprisingly, DMSCs express membrane-bound ENG (CD105). PE-affected DMSCs (PE-DMSCs) are abnormal and due to reduced extravillous invasion, more of them are present, but the significance of this is not known. MethodsDMSCs were isolated and characterised from normotensive control and severe-PE placentae. Extracellular vesicle (EV) types, shed microvesicles (sMV) and exosomes, were isolated from DMSC conditioned media (DMSCCM), respectively. Secretion of ENG by DMSCs was assessed by ELISA of DMSCCM, with and without EV depletion. The effects of reducing ENG concentration, by blocking antibody, on human umbilical vein endothelial cell (HUVEC) attachment were assessed by xCELLigence real-time functional assays. ResultsENG was detected in DMSCCM and these levels significantly decreased when depleted of exosomes and sMV. There was no significant difference in the amount of ENG secreted by control DMSCs and PE-DMSCs. Blocking ENG in concentrated DMSCCM, used to treat HUVECs, improved endothelial cell attachment. DiscussionIn normotensive pregnancies, DMSC secretion of ENG likely has a beneficial effect on endothelial cells. However, in PE pregnancies, shallow invasion of the spiral arterioles exposes more PE-DMSC derived sources of ENG (soluble and EV). The presence of these PE-DMSCs in the vascular niche contributes to endothelial cell dysfunction.