Previous Early-onset Preeclampsia Research Articles

Markers of systemic endotheliosis in early-onset preeclampsia relapse

Aim: to assess the blood level of biological endothelial damage markers in women with previous early-onset preeclampsia (еPE) during both the preconception (PC) stage and the first trimester of pregnancy.Materials and Methods. A prospective single-center cohort study was conducted. The control group comprised 40 women with uncomplicated pregnancies. The observation group consisted of 97 patients with a history of ePE, stratified based on pregnancy outcome into the comparison group (n = 59) characterized by a favorable gestational course, and the main group (n = 38) with relapsed еPE (30 patients were excluded from the study). Markers of systemic endotheliosis were determined in women at the PC stage and at 11–13 weeks of gestation: endothelin-1 (ET-1) and endothelial extracellular vesicles (EVs; CD-144).Results. At the PC stage, women in the control group and patients from the comparison group had comparable median (Me) ET-1 levels – 0.39 and 0.40 pmol/ml (p = 0.5935), respectively; at the same time, patients with relapsed еPE vs. control group had it significantly elevated (Me = 0.55 pmol/ml; p = 0.0382). At gestational age of 11–13 weeks, ET-1 level was significantly higher in the group with relapsed еPE (Me = 0.93 pmol/ml) than in control group (Me = 0.29 pmol/ml; p < 0.0001) and comparison group (Me = 0.42 pmol/ml; p = 0.0003). No significant changes in E-EVs (CD-144) level at various PС stages were observed, whereas in the study groups such parameters remained differed.Conclusion. Biological markers evidencing about systemic endothelial dysfunction/destruction – ET-1 and E-EVs (CD-144) in patients with previous ePE can be considered as predictive tests of disease relapse with an accuracy of 63.5 % and 83.0 % at the PС stage and 85.7 % and 94.2 % at gestational age of 11–13 weeks, respectively.

Circulating cardiovascular biomarkers during and after preeclampsia: Crosstalk with placental function?

Cardiovascular disease (CVD) is the leading cause of death in women, yet sex-specific risk factors remain understudied. Preeclampsia and other adverse pregnancy outcomes imply an increased maternal cardiovascular risk. We hypothesized that cardiac troponin T (cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) are increased in such pregnancies and correlate with markers of placental dysfunction. We also investigated these cardiovascular biomarkers 1 or 3years postpartum. Prior to delivery, we included serum from 417 pregnant women: 55 early-onset preeclampsia (EO-PE), 63 late-onset preeclampsia (LO-PE), 30 gestational hypertension (GH) and 269 healthy controls. Postpartum, we included 341 women 1 or 3years after delivery: 26 EO-PE, 107 LO-PE, 61 GH, and 147 healthy pregnancies. Prior to delivery, median cTnT and NT-proBNP concentrations were higher in women with EO-PE, LO-PE, or GH than in controls. Median GDF-15 was higher in EO-PE and LO-PE compared to controls. Postpartum, GDF-15 was elevated in women with previous EO-PE. Markers of placental dysfunction correlated with CVD biomarkers in pregnancy, but not postpartum. Our findings underscore the cardiovascular burden of hypertensive disorders of pregnancy and the crosstalk with placental function. The upregulation of circulating GDF-15 following early-onset preeclampsia is in line with the epidemiological excessive risk of premature CVD in this group of women. GDF-15 may be explored for targeting postpartum women with most to gain from intensified preventive follow-up for CVD.

Cardiovascular events following pregnancy complicated by pre-eclampsia with emphasis on comparison between early- and late-onset forms: systematic review and meta-analysis.

To elucidate whether pre-eclampsia (PE) and the gestational age at onset of the disease (early- vs late-onset PE) have an impact on the risk of long-term maternal cardiovascular complications. MEDLINE, EMBASE and Scopus databases were searched until 15 April 2020 for studies evaluating the incidence of cardiovascular events in women with a history of PE, utilizing combinations of the relevant MeSH terms, keywords and word variants for 'pre-eclampsia', 'cardiovascular disease' and 'outcome'. Inclusion criteria were cohort or case-control design, inclusion of women with a diagnosis of PE at the time of the first pregnancy, and sufficient data to compare each outcome in women with a history of PE vs women with previous normal pregnancy and/or in women with a history of early- vs late-onset PE. The primary outcome was a composite score of maternal cardiovascular morbidity and mortality, including cardiovascular death, major cardiovascular and cerebrovascular events, hypertension, need for antihypertensive therapy, Type-2 diabetes mellitus, dyslipidemia and metabolic syndrome. Secondary outcomes were the individual components of the primary outcome analyzed separately. Data were combined using a random-effects generic inverse variance approach. MOOSE guidelines and the PRISMA statement were followed. Seventy-three studies were included. Women with a history of PE, compared to those with previous normotensive pregnancy, had a higher risk of composite adverse cardiovascular outcome (odds ratio (OR), 2.05 (95% CI, 1.9-2.3)), cardiovascular death (OR, 2.18 (95% CI, 1.8-2.7)), major cardiovascular events (OR, 1.80 (95% CI, 1.6-2.0)), hypertension (OR, 3.93 (95% CI, 3.1-5.0)), need for antihypertensive medication (OR, 4.44 (95% CI, 2.4-8.2)), dyslipidemia (OR, 1.32 (95% CI, 1.3-1.4)), Type-2 diabetes (OR, 2.14 (95% CI, 1.5-3.0)), abnormal renal function (OR, 3.37 (95% CI, 2.3-5.0)) and metabolic syndrome (OR, 4.30 (95% CI, 2.6-7.1)). Importantly, the strength of the associations persisted when considering the interval (< 1, 1-10 or > 10 years) from PE to the occurrence of these outcomes. When stratifying the analysis according to gestational age at onset of PE, women with previous early-onset PE, compared to those with previous late-onset PE, were at higher risk of composite adverse cardiovascular outcome (OR, 1.75 (95% CI, 1.0-3.0)), major cardiovascular events (OR, 5.63 (95% CI, 1.5-21.4)), hypertension (OR, 1.48 (95% CI, 1.3-1.7)), dyslipidemia (OR, 1.51 (95% CI, 1.3-1.8)), abnormal renal function (OR, 1.52 (95% CI, 1.1-2.2)) and metabolic syndrome (OR, 1.66 (95% CI, 1.1-2.5). Both early- and late-onset PE represent risk factors for maternal adverse cardiovascular events later in life. Early-onset PE is associated with a higher burden of cardiovascular morbidity and mortality compared to late-onset PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

72. Early onset preeclampsia predicts increased cardiovascular risk 1 year postpartum

Objective/hypothesis Cardiovascular follow-up of women with previous hypertensive disorder of pregnancy (HDP) has been suggested, as they are at increased long-term CVD risk. There is however no consensus on when to start follow-up of women who regained normal blood pressure postpartum. We assessed at 1 year postpartum if a previous HDP predicts cardiovascular risk beyond risk factors generally known. Methods Gestational hypertension (GH) was defined as de novo hypertension ⩾gestational week (GW) 20 and preeclampsia (PE) was defined as GH with new-onset proteinuria. Early-onset PE was defined as PE with delivery Linear regression was used to measure associations between the FRS and previous HDP and adjusted for body mass index, age, smoking, premature cardiovascular disease in a 1st degree relative, and blood pressure at beginning of index pregnancy. P Results Framingham Risk Scores according to pregnancy diagnosis. Discussion Early-onset PE independently confers increased cardiovascular risk 1 year postpartum. Women with previous early-onset PE should receive early follow-up for prevention of cardiovascular disease.

Early gestational age at preeclampsia onset is associated with subclinical atherosclerosis 12 years after delivery.

Women with a history of preeclampsia have increased risk of cardiovascular disease later in life. However, it is unclear whether early gestational age at preeclampsia onset is associated with higher cardiovascular disease risk. This study aimed to test the association between gestational age at preeclampsia onset (including the early-onset/late-onset preeclampsia distinction) and subclinical atherosclerosis and arterial stiffness in age-matched women 12 years after index pregnancy. Eligible participants were identified in two Danish registries. Main outcome measures were carotid plaque presence, carotid intima-media thickness, aortic pulse wave velocity, and augmentation index adjusted for heart rate. Twenty-four women with previous early-onset preeclampsia, 24 with previous late-onset preeclampsia and 24 with previous normotensive pregnancies were included after matching on age (±2 years) and time since delivery (±1 year). In all outcome measures, the early-onset group had the highest percentage or mean value. In the adjusted analysis, the early-onset group significantly differed from the late-onset group in all outcome measures except aortic pulse wave velocity. The early-onset group also had significantly higher carotid intima-media thickness (average and left) compared with the normotensive group. Gestational age at preeclampsia onset as a continuous variable was significantly associated to both carotid plaque presence and carotid intima-media thickness (average and right). Gestational age at preeclampsia onset is negatively associated with markers of subclinical atherosclerosis 12 years after delivery. Potentially, gestational age at preeclampsia onset might be helpful in directing cardiovascular disease prevention after preeclampsia.

Cardiovascular Disease Risk Factors in Women With a History of Early-Onset Preeclampsia

To assess the prevalence of established cardiovascular disease risk factors and to estimate 10-year absolute risk of cardiovascular disease after early-onset preeclampsia. We assessed major cardiovascular disease risk factors in 243 primiparous women with a history of early-onset preeclampsia (delivery at less than 34 weeks of gestation) at least 6 months after delivery; 374 healthy nonpregnant women of similar age served as a reference group. After adjustment for age, we observed significantly higher means for body mass index, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, glucose, and lower mean high-density lipoprotein cholesterol (all P<.01) in women with previous early-onset preeclampsia compared with the reference group. Prevalence of the metabolic syndrome was 15.2% compared with 4.3% (P<.001), two or more major cardiovascular disease risk factors were present in 51.0% compared with 26.5%, and three or more risk factors were present in 18.9% compared with 6.4%, respectively. Mean estimated 10-year cardiovascular disease risks by the Framingham Risk Score were 1.08% (95% confidence interval 1.04-1.12) and 1.01% (95% CI 1.00-1.01; P<.001) for the difference. Women with a history of early-onset preeclampsia have a high prevalence of several major cardiovascular disease risk factors. Although the estimated 10-year cardiovascular disease risk is low (less than 5%) after delivery, cardiovascular disease risk is expected to increase rapidly with increasing age. II.

OS023. Postpartum cardiovascular disease risk factors in women with ahistory of early onset preeclampsia, late onset preeclampsia and pregnancy induced hypertension

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women. Epidemiological studies have shown an increased risk of a CVD event in women who have had a hypertensive disorder in one of their previous pregnancies. These data also suggest that these increased risks are associated with severity and time of onset of pre-eclampsia. Risk factors for CVD have not yet been compared between women who experienced early versus late and mild versus severe hypertensive disorders of pregnancy. In this study we compared classic CVD risk factors of postpartum women with previous early-onset preeclampsia (EOPE), late onset pre-eclampsia (LOPE) and pregnancy induced hypertension (PIH). A total of 81 women with previous EOPE (delivery required ⩽34weeks), 76 with LOPE (delivery ⩾36weeks) and 229 with PIH were included along with 79 healthy controls. Statistical analyses were performed using generalized linear models in PASW statistics 17.0, SPSS Inc. Adjusted means of blood pressure, fasting plasma glucose levels and LDL levels were significantly increased after all hypertensive disorders of pregnancy compared to controls. This increase of CVD risk factors was significantly correlated with severity and time of onset of the disease (Table 1). The prevalence of metabolic syndrome (BMI>30kg/m(2) and ⩾2 of the following; triglycerides ⩾150mg/dl, HDL cholesterol ⩾50mg/dl, systolic blood pressure ⩾130 or diastolic blood pressure ⩾85 and fasting plasma glucose levels ⩾100mg/dl) did not differ between the study groups; women who had PIH had the highest number of components of the metabolic syndrome (). These results further establish the predisposition to CVD in women with previous pre-eclampsia or PIH. EOPE is associated with a more pronounced CVD risk factor profile than LOPE or PIH, which may explain the previously described higher CVD event risk.

PP032. Unique features of long-term cardiovascular phenotype in young women with early-onset pre-eclampsia

Early-onset preeclampsia is associated with a greater risk of cardiovascular disease than late-onset preeclampsia. We tested the hypothesis that young women, with previous early-onset preeclampsia, have unique differences in long term cardiovascular phenotype compared to late-onset preeclampsia or normal pregnancy. 140 women (mean age 40 yrs) were followed up 6-13years following pregnancy. 90 had had preeclampsia (45 early onset (before 34 weeks of gestation), 45 late onset) and 50 had normotensive uncomplicated pregnancies. Women with cardiovascular risk factors present before pregnancy were excluded. Fasting lipids, glucose, insulin and circulating cytokines were measured. Central blood pressure (BP) and arterial stiffness (pulse wave velocity (PWV)/augmentation index (AI)) were assessed by applanation tonometry, common carotid intima media thickness (cIMT) by ultrasound and cutaneous capillary density by intravital microscopy. 46 women returned for assessment of cardiac structure and function by magnetic resonance and echocardiography as well as ambulatory blood pressure monitoring. All women with a previous history of preeclampsia had 5-10mmHg higher peripheral and central BP (P<0.001) as well as elevated total: HDL cholesterol (P<0.003), insulin resistance (P<0.04) and circulating TNFα (P<0.007). They also had increased arterial stiffness (P<0.04) and cIMT (P<0.005). Cardiac size and systolic function were preserved but there was evidence of abnormal diastolic relaxation (E/E' -P<0.04). In contrast early-onset preeclampsia was associated with characteristic differences in peri-pregnancy blood pressure, long term ambulatory measures and microvascular function. Early onset preeclampsia is associated with unique features in long term cardiovascular phenotype. Pregnancy disease characteristics may identify women at greatest potential benefit from monitoring and primary prevention.

Vascular Dysfunction in Women With a History of Preeclampsia and Intrauterine Growth Restriction

Background— Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Methods and Results— Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate–induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angiogenic factors (vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin). Flow-mediated vasodilatation was significantly reduced in women with previous early-onset preeclampsia and intrauterine growth restriction compared with women with previous late-onset preeclampsia and control subjects (3.2±2.7% and 2.1±1.2% versus 7.9±3.8% and 9.1±3.5%, respectively; P &lt;0.0001). Flow-independent vasodilatation was similar among all groups. Similarly, the radial augmentation index was significantly increased among women with previous early-onset preeclampsia and intrauterine growth restriction, but not among late preeclamptic women and control subjects ( P =0.0105). Circulating angiogenic factors were similar in all groups. Conclusion— Only women with a history of early-onset preeclampsia or intrauterine growth restriction without preeclampsia exhibit impaired vascular function, which might explain their predisposition to placental disease and their higher risk of future vascular disease.

Editor’s Choice

Editor’s Choice

Simple Prepregnant Prediction Rule for Recurrent Early-onset Hypertensive Disease in Pregnancy

We aimed to develop a simple clinically useful prediction rule for early-onset recurrent preeclampsia and/or HELLP syndrome. Women with previous early-onset preeclampsia and/or HELLP, enrolled between 1996 and 2007, and a subsequent ongoing pregnancy were included. Prepregnant cardiovascular, metabolic, renal, and clotting parameters were evaluated as potential predictors for recurrent disease by logistic regression analysis. Early-onset preeclampsia and/or HELLP recurred in 16 (9%) of 186 next pregnancies. The prediction model included high-density lipoprotein (mmol/L) and 24-hour urinary total protein excretion (mg/mmol creatinine). The receiver operating characteristic area was 0.77 (95% confidence interval: 0.68-0.87). Predictive sensitivity and specificity were 94% (69%-99%) and 53% (45%-60%), respectively. Nearly 50% of the women could be classified as having <1% risk of recurrent early-onset disease. The prediction rule identified, with clinically relevant predictive capacity, those women at very low risk for recurrent early-onset disease.

18: Classic risk factors predictive of first cardiovascular events in women with a history of early-onset preeclampsia: Opportunities for primary prevention

WOMEN WITH A HISTORY OF EARLY-ONSET PREECLAMPSIA: OPPORTUNITIES FOR PRIMARY PREVENTION BAS VAN RIJN, HEIN BRUINSE, MARK ROEST, HIERONYMUS VOORBIJ, MICHIEL BOTS, ARIE FRANX, University Medical Center Utrecht, Division of Perinatology & Gynecology, Utrecht, Netherlands, University Medical Center Utrecht, Department of Clinical Chemistry, , Netherlands, University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands, St. Elisabeth Ziekenhuis, Obstetrics and Gynaecology, Tilburg, Netherlands OBJECTIVE: Women with a history of early-onset preeclampsia are at increased risk of developing major cardiovascular disease (CVD) related events, that have a detrimental effect on their long-term health and life expectancy. In this follow-up study, we measured established risk factors predictive of first CVD events after early-onset preeclampsia. STUDY DESIGN: Over a 10-year interval, 243 primiparous women with a history of early-onset preeclampsia (delivery 34 weeks gestation) were included and tested for major cardiovascular risk factors at least six months after delivery, in addition to a population-based control group of 374 healthy non-pregnant women. Women with chronic hypertension were excluded. RESULTS: Mean age was 30.5 years for cases compared to 28.3 years for controls (P .001). After adjustment for age, we observed significantly increased mean values for weight (P .002), body-mass index (P .001), systolic blood pressure (P .001), diastolic blood pressure (P .001), total cholesterol (P .006), LDL cholesterol (P .001), triglycerides (P .027), fasting blood glucose (P .001), and lower HDL cholesterol (P .001) in women with previous early-onset preeclampsia. No difference was found for height, smoking, diabetes, and ethnicity. Estimated 10-year risk of first CVD events by Framingham Risk Scores remained 10% for all women (low-risk). Nonetheless, at mean (SD) 0.7 (1.0) years after early-onset preeclampsia, 15% of women met the criteria for metabolic syndrome. Additionally, 89% of women exhibited 1, 51% of women 2 and 19% of women 3 major CVD risk factors. CONCLUSION: The majority of women with a history of early-onset preeclampsia exhibit at least one modifiable risk factor for future CVD. Although most of these women are classified as low-risk according to the current AHA guidelines, this is mainly due to their young age masking other, mostly modifiable, major risk factors. Our data thus support life-style intervention programs aimed at primary prevention of CVD in women with a history of early-onset preeclampsia.

Maternal serum activin A is not elevated before preeclampsia in women who are at high risk

Objective: The purpose of this study was to determine whether, in women who are at high risk of the development of preeclampsia, serum activin A concentrations are elevated before the disease and whether activin A is a useful predictor of preeclampsia. Study Design: Sera were collected on five occasions throughout pregnancy from women with chronic hypertension, renal disease, or previous early-onset preeclampsia (n = 80 women). Women were classified as control subjects (normotensive or stable chronic hypertension), gestational hypertensive, or preeclamptic (de novo or superimposed). Serum activin A concentrations were measured by immunoassay. Differences in activin A concentrations between groups were analyzed with the use of a mixed-models procedure; screening test characteristics were calculated. Results: Twenty-six women (33%) had gestational hypertension, and 17 women (21%) had preeclampsia or superimposed preeclampsia. Serum activin A levels increased with gestation in all groups (P =.0001), but there were no significant difference in activin A levels between groups (P =.75). Conclusion: In women who were at high risk of the development of preeclampsia, serum activin A levels are not elevated with preeclampsia. Activin A is not a useful predictor of preeclampsia in this setting. (Am J Obstet Gynecol 2003;188:·807-11.)