Unexplained recurrent pregnancy loss and markers of arterial vascular health: An experimental case-control study.

OBJECTIVE: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise. DESIGN: Experimental case-control pilot study. SETTING: University medical centre in the Netherlands. POPULATION: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies. METHODS: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training. MAIN OUTCOME MEASURES: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss. RESULTS: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss. CONCLUSIONS: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.

The efficacy of emergency cervical cerclage in singleton and twin pregnancies: a systematic review with meta-analysis.

OBJECTIVE: An emergency (rescue) cervical cerclage can be offered to pregnant women presenting with dilatation and prolapsed membranes in the second trimester of pregnancy because of cervical insufficiency. This study aimed to investigate the effectiveness of an emergency cerclage in both singleton and twin pregnancies in the prevention of extreme premature birth. DATA SOURCES: We performed a systematic literature search in PubMed and Embase from inception to June 2022 for transvaginal cervical emergency cerclages. STUDY ELIGIBILITY CRITERIA: All studies on transvaginal cervical emergency cerclages with at least 5 patients and reporting survival were included. METHODS: Included studies were assessed for quality and risk of bias with an adjusted Quality In Prognosis Studies tool. Random-effects meta-analyses and meta-regressions were performed for the primary outcome: survival. RESULTS: Our search yielded 96 studies, incorporating 3239 women, including 14 studies with an expectant management control group, incorporating 746 women. Overall survival after cervical emergency cerclage was 74%, with a fetal survival of 88% and neonatal survival of 90%. Singleton and twin pregnancies showed similar survival, with a pregnancy prolongation of 52 and 37 days and a gestational age at delivery of 30 and 28 weeks, respectively. Meta-regression analyses indicated a significant inverse association between mean gestational age at diagnosis and pregnancy prolongation and no association between dilatation or gestational age at diagnosis and gestational age at delivery. Compared with expectant management, emergency cerclage significantly increased overall survival by 43%, fetal survival by 17% and neonatal survival by 22%, along with a significant pregnancy prolongation of 37 days and reduction in delivery at <28 weeks of gestation of 55%. These effects were more profound in singleton pregnancies than in twin pregnancies. CONCLUSION: This systematic review indicates that, in pregnancies threatened by extreme premature birth because of cervical insufficiency, emergency cerclage leads to significantly higher survival, accompanied by significant pregnancy prolongation and reduction in delivery at <28 weeks of gestation, compared with expectant management. The mean gestational age at delivery was 30 weeks, independent of dilatation or gestational age at diagnosis. Survival was similar for singleton and twin pregnancies, implying that emergency cerclage should be considered in both.

The effectiveness of transabdominal cerclage placement via laparoscopy or laparotomy: a systematic review and meta-analysis.

OBJECTIVE: Failure or technical impossibility to place a prophylactic transvaginal cerclage in women with cervical insufficiency justifies the need for an abdominal cerclage. In this systematic review and meta-analysis, we studied the obstetrical and surgical outcomes of laparoscopic and open laparotomy abdominal cerclage approaches performed before (interval) or during pregnancy. DATA SOURCES: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for studies on laparoscopic and open laparotomy abdominal cerclage placement in February 2022. STUDY ELIGIBILITY CRITERIA: All studies on laparoscopic or open laparotomy placement of an abdominal cerclage with at least 2 patients that reported on our primary outcomes were included. METHODS: All included studies were assessed for quality and risk of bias with an adjusted Quality in Prognosis Study tool. Random effects meta-analyses were performed for the primary outcomes, namely fetal survival and gestational age at delivery. RESULTS: Our search yielded 83 studies with a total of 3398 patients; 1869 of those underwent laparoscopic cerclage placement and 1529 underwent open laparotomy placements. No studies directly compared the 2 cerclage approaches. The survival (overall, 91.2%) and gestational age at delivery (overall, 36.6 weeks) were not statistically different between the approaches. For the procedure during pregnancy, the laparoscopic group showed significantly less blood loss >400 mL (0% vs 3%), a slightly lower procedure-related fetal loss (0% vs 1%), a shorter hospital stay but a longer operation duration than the open laparotomy group. For the interval cerclages, the laparoscopic group showed significantly fewer wound infections (0% vs 3%) and a shorter hospital stay than the open laparotomy group, but showed comparable offspring preterm birth and survival rates. CONCLUSION: Based on indirect comparisons, the laparoscopic and open laparotomy abdominal cerclage placements at interval or during pregnancy produced similar outcomes in terms of survival and gestational age at delivery. There are some small differences in perioperative care, surgical complications, interventions, and complications during pregnancy. This implies that both methods of abdominal cerclage placement have high success rates and thus we cannot conclude that one of the methods is superior for the placement of an abdominal cerclage.

Comparison of three definitions of metabolic syndrome and relation to risk of recurrent preeclampsia.

Objective. To determine the prevalence of metabolic syndrome in formerly preeclamptic women according to three definitions of metabolic syndrome (World Health Organization [WHO], International Diabetes Federation [IDF], and Third Adult Treatment Panel updated [ATPIII]), to evaluate agreement amongst definitions and to compare the risk of recurrent preeclampsia. Methods. In 197 women with a history of preeclampsia, we determined presence of metabolic syndrome using WHO, IDF, and ATPIII criteria. We evaluated agreement amongst definitions by using Kappa statistics. The prevalence of recurrent preeclampsia was compared between women with and without inter-pregnancy metabolic syndrome, according to the three definitions. Results. A total of 40 (20%), 46 (23%), and 31 (16%) of women with previous preeclampsia were classified as having metabolic syndrome postpartum according to WHO, IDF, and ATPIII criteria, respectively. Agreement among criteria was considered substantial between WHO and IDF (κ = 0.64, 95% CI 0.53-0.79), WHO and ATPIII (κ = 0.74, 95% CI 0.62-0.86), and IDF and ATPIII (κ = 0.66, 95% CI 0.51-0.77). The prevalence of recurrent preeclampsia was 45% versus 17% in women with and without inter-pregnancy metabolic syndrome according to the WHO definition (P < 0.001), 26% versus 21% according to the IDF criteria (P = 0.16), and 39% versus 20% according to the ATPIII definition (P = 0.02). Conclusions. Agreement among WHO, IDF, and ATPIII criteria of metabolic syndrome in women after preeclampsia is considered substantial. The risk of recurrent preeclampsia is almost one out of two in women with inter-pregnancy metabolic syndrome according to the WHO criteria.

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology.

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants.

Low Plasma Volume and Increased Pressure Load Relate to Concentric Left Ventricular Remodeling After Preeclampsia: A Longitudinal Study.

Background During uncomplicated pregnancy, left ventricular remodeling occurs in an eccentric way. In contrast, during preeclamptic gestation, the left ventricle hypertrophies concentrically, concurrent with loss in circulatory volume and increased blood pressure. Concentric cardiac structure persists in a substantial proportion of women and may be associated with pressure and volume load after preeclampsia. We hypothesize that low volume load, as indicated by plasma volume (PV) after preeclampsia and increased pressure load, is associated with remote concentric remodeling. Methods and Results In this longitudinal cohort study, we included 100 formerly preeclamptic women. Two visits were performed: at 0.8 years postpartum and at 4.8 years postpartum. During visit 1, we measured blood pressure and PV (I125 dilution technique, low PV ≤48 mL/kg lean body mass). During the second visit, we assessed cardiac geometry by cardiac ultrasound. Concentric remodeling was defined as relative wall thickness >0.42 and left ventricular mass index ≤95 g/m2. We adjusted multivariable analysis for primiparity, systolic blood pressure, PV mL/kg lean body mass, and antihypertensive medication at visit 1. Low PV is associated with remote concentric remodeling (odds ratio [OR], 4.37; 95% CI, 1.06-17.40; and adjusted OR, 4.67; 95% CI, 1.02-21.42). Arterial pressure load (systolic, diastolic, and mean arterial pressure) is also associated with development of concentric remodeling (OR, 1.15 [95% CI, 0.99-1.35]; OR, 1.24 [95% CI, 0.98-1.58]; and OR, 1.20 [95% CI, 0.98-1.47], respectively). Conclusions In former preeclamptic women, development toward left ventricular concentric remodeling is associated with low volume load and increased pressure load.

Metabolic Syndrome After Preeclamptic Pregnancy: A Longitudinal Cohort Study.

INTRODUCTION: History of preeclampsia increases the risk of cardiovascular disease in women. Most formerly, preeclamptic women have generally one or even more traditional cardiovascular and/or cardiometabolic risk factors consistent with metabolic syndrome in the first year after delivery. The objective of this study was to analyze the prevalence and persistence of risk factors contributing to metabolic syndrome for the course of years after preeclamptic pregnancy. METHODS: In a longitudinally cohort study, 107 formerly preeclamptic women were assessed for traditional risk factors (insulin resistance, obesity, dyslipidemia, hypertension, and microalbuminuria) of metabolic syndrome (World Health Organization criteria) at two time points: at 3-30 months postpartum (visit 1) and 24-65 months later (visit 2). RESULTS: At visit 1, 10 of 107 (9%) formerly preeclamptic women had metabolic syndrome, and at visit 2, 14 of 107 (13%) (p = 0.21) had metabolic syndrome. Most formerly, preeclamptic women (90%) did not change their metabolic syndrome status over the years, as 7 of 107 (7%) women had persistent metabolic syndrome and 90 of 107 (84%) women did not meet the criteria for metabolic syndrome on either visit. In 3 of 107 (3%) formerly preeclamptic women, metabolic syndrome disappeared over time, whereas 7 of 107 (7%) preeclamptic women developed it. CONCLUSION: The presence or absence of metabolic syndrome remains unchanged in 90% of formerly preeclamptic women for the first years after preeclampsia. Only in 10% of women, metabolic syndrome developed or recovered, indicating that early screening within the first year postpartum in these women effectively detects those with metabolic syndrome who are known to be at increased risk for cardiovascular disease later in life.

Improvements in fitness are not obligatory for exercise training-induced improvements in CV risk factors.

The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center-based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8-52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high-density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P > 0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training-induced improvements in cardiovascular risk factors.

Endothelial and kidney function in women with a history of preeclampsia and healthy parous controls: A case control study.

INTRODUCTION: Preeclampsia (PE) is a pregnancy related endothelial disease characterized by hypertension and albuminuria. Postpartum endothelial dysfunction often persists in these women. We postulate that in women with a history of PE reduced endothelial dependent vasodilation coincides with attenuated kidney function, as both reflect endothelial dysfunction. METHODS: We assessed endothelial and kidney function in women with a history of PE (n=79) and uncomplicated pregnancies (n=49) at least 4years postpartum. Women with hypertension, diabetes or kidney disease prior to pregnancy were excluded. Brachial artery flow mediated dilatation (FMD) was measured and analysed by a custom designed edge-detection and wall-tracking software. We measured albumin and creatinine levels in a 24-h urine sample and calculated glomerular filtration rate (GFR) by CKD-EPI. RESULTS: Women with a history of PE had lower FMD but comparable GFR and albumin creatinine ratio (ACR) compared with controls. Independent of obstetric history, in both controls and women with a history of PE respectively, GFR (r=0.19, p=0.17 and r=0.12, p=0.29) and albumin creatinine ratio (r=0.07, p=0.62 and r=0.06 p=0.57) did not correlate with FMD. CONCLUSION: At least 4years after pregnancy, women with a history of PE demonstrated decreased flow mediated dilatation when compared to healthy parous controls. In this study, decreased flow mediated dilation however did not coincide with decreased kidney function.

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization.

History of preeclampsia is more predictive of cardiometabolic and cardiovascular risk factors than obesity.

OBJECTIVE: To determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of BMI. STUDY DESIGN: In a retrospective case-control study we compared 90 formerly preeclamptic women, divided in 3 BMI-classes (BMI 19.5-24.9, 25.0-29.9, ≥30.0kg/m(2)) to 30 controls, matched for BMI, age and parity. Cardiometabolic and cardiovascular risk factors (WHO-criteria) were tested 6-18 months post partum. Statistical analysis included unpaired t-tests, Mann-Whitney U test, or Chi square test and two-way ANOVA. RESULTS: Constituents of the metabolic syndrome (glucose, insulin, HOMAIR, HDL-cholesterol, triglycerides, blood pressure, micro-albuminuria) were higher in formerly preeclamptic women than in BMI-matched controls. Resultantly, traditional risk factors were more prevalent in formerly preeclamptic women than in controls (insulin resistance 80% vs 30%, dyslipidemia 52% vs 3%, hypertension 24% vs 0%, micro-albuminuria 30% vs 0%). Cardiometabolic risk factors increased with BMI, to the same extent in both groups. Formerly preeclamptic women had metabolic syndrome more often than their BMI-matched controls (38% vs 3%, p<0.001). CONCLUSION: Traditional risk factors of the metabolic syndrome are more prevalent in formerly preeclamptic women than in BMI-matched controls and increase with BMI to the same extent in both groups. A history of preeclampsia seems to be a stronger indicator of cardiovascular risk than obesity per se.

Low Plasma Volume in Normotensive Formerly Preeclamptic Women Predisposes to Hypertension.

Formerly preeclamptic women are at risk for cardiovascular disease. Low plasma volume may reflect latent hypertension and potentially links preeclampsia with chronic cardiovascular disease. We hypothesized that low plasma volume in normotensive formerly preeclamptic women predisposes to hypertension. We longitudinally studied n=104 formerly preeclamptic women in whom plasma volume was measured 3 to 30 months after the preeclamptic pregnancy. Cardiovascular variables were assessed at 2 points in time (3-30 months postpartum and 2-5 years thereafter). Study population was divided into low plasma volume (≤1373 mL/m(2)) and normal plasma volume (>1373 mL/m(2)). Primary end point was hypertension at the second visit: defined as ≥140 mm Hg systolic or ≥90 mm Hg diastolic. Secondary outcome of this study was change in traditional cardiovascular risk profile between visits. Variables correlating univariately with change in blood pressure between visits were introduced in regression analysis. Eighteen of 104 (17%) formerly preeclamptic women who were normotensive at first visit had hypertension at second evaluation 2 to 5 years later. Hypertension developed more often in women with low plasma volume (10/35 [29%]) than in women with normal plasma volume (8/69 [12%]; odds ratio, 3.2; 95% confidence interval, 1.4-8.6). After adjustments, relationship between plasma volume status and subsequent hypertension persisted (adjusted odds ratio, 3.0; 95% confidence interval, 1.1-8.5). Mean arterial pressure at second visit correlated inverse linearly with plasma volume (r=-0.49; P<0.01). Initially normotensive formerly preeclamptic women have 17% chance to develop hypertension within 5 years. Women with low plasma volume have higher chance to develop hypertension than women with normal plasma volume. Clinically, follow-up of blood pressure seems warranted in women with history of preeclampsia, even when initially normotensive.

Aerobic Exercise Training in Formerly Preeclamptic Women: Effects on Venous Reserve.

UNLABELLED: In women with a history of preeclampsia, low plasma volume (≤1373 mL/m(2)) is associated with recurrent preeclampsia and chronic hypertension. Interventions that improve volume reserve may reduce these risks in formerly preeclamptic women. In this study, we examined the effects of aerobic exercise training on venous reserves in 24 normotensive formerly preeclamptic women and 20 controls. Before and after 12-week aerobic exercise training, we measured plasma volume with albumin indicator dilution technique and venous compliance with venous occlusion plethysmography. Venous compliance and hemodynamic responses were assessed dynamically during graded head-up tilt (HUT). Formerly preeclamptic women had lower pretraining plasma volume and venous compliance than controls (1348±78 versus 1529±112 mL/m(2); P<0.01 and 0.04±0.02 versus 0.07±0.01 mL·dL(-1)·mm Hg(-1); P<0.01, respectively). Blood pressure decreased comparably between groups in response to HUT (P=0.11); the increase in heart rate in response to HUT was however more pronounced in preeclamptic women than in controls (P=0.01) Training increased plasma volume comparably in both groups (+180 versus +135 mL/m(2), P=0.22) and similarly physical fitness (+3.4 and +3.7 mL·min(-1)·kg(-1), P=0.43). Venous compliance increased twice as much in formerly preeclamptic women than in controls (supine +0.02 versus +0.01 mL·dL(-1)·mm Hg(-1); P<0.01). After training, HUT decreased mean blood pressure comparable with pretraining responses in both groups, whereas both groups fulfilled the HUT testing at a persistently lower heart rate. These results demonstrate that 12 weeks of aerobic exercise training improve venous reserve in postpartum women. Training normalized plasma volume and venous compliance in formerly preeclamptic women to pretraining levels of controls. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900458.

Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors.

The objectives of our study were to examine 1) the proportion of responders and nonresponders to exercise training in terms of vascular function; 2) a priori factors related to exercise training-induced changes in conduit artery function, and 3) the contribution of traditional cardiovascular risk factors to exercise-induced changes in artery function. We pooled data from our laboratories involving 182 subjects who underwent supervised, large-muscle group, endurance-type exercise training interventions with pre-/posttraining measures of flow-mediated dilation (FMD%) to assess artery function. All studies adopted an identical FMD protocol (5-min ischemia, distal cuff inflation), contemporary echo-Doppler methodology, and observer-independent automated analysis. Linear regression analysis was used to identify factors contributing to changes in FMD%. We found that cardiopulmonary fitness improved, and weight, body mass index (BMI), cholesterol, and mean arterial pressure (MAP) decreased after training, while FMD% increased in 76% of subjects (P < 0.001). Training-induced increase in FMD% was predicted by lower body weight (ß = -0.212), lower baseline FMD% (ß = -0.469), lower training frequency (ß = -0.256), and longer training duration (ß = 0.367) (combined: P < 0.001, r = 0.63). With the exception of a modest correlation with total cholesterol (r = -0.243, P < 0.01), changes in traditional cardiovascular risk factors were not significantly related to changes in FMD% (P > 0.05). In conclusion, we found that, while some subjects do not demonstrate increases following exercise training, improvement in FMD% is present in those with lower pretraining body weight and endothelial function. Moreover, exercise training-induced change in FMD% did not correlate with changes in traditional cardiovascular risk factors, indicating that some cardioprotective effects of exercise training are independent of improvement in risk factors.

Retrograde shear rate in formerly preeclamptic and healthy women before and after exercise training: relationship with endothelial function.

Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this relationship is altered by exercise training. Formerly PE women (32 ± 4 yr, n = 20) and controls (32 ± 4 yr, n = 20), all 6-12 mo postpartum, performed 12-wk aerobic exercise training. We measured brachial artery shear rate (SR) and endothelial function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed power spectral analysis of heart rate variability and calculated low-frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between groups, while retrograde SR was significantly higher and FMD% lower in PE women compared with controls (both P < 0.05). Retrograde shear correlated strongly with FMD% in PE women and controls (P < 0.05). LF/HF ratio inversely correlated with brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls. Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF ratios similarly in both groups (all P < 0.05). Training-induced changes in retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial artery retrograde SR relates to lower brachial artery endothelial function, in both controls and formerly PE women. Exercise training improves retrograde SR, while the magnitude of this change correlated strongly with improvements in FMD and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training on endothelial health may, at least partly, be related to retrograde shear rate.

Cardiovascular effects of aerobic exercise training in formerly preeclamptic women and healthy parous control subjects.

OBJECTIVE: Women who have had preeclampsia demonstrate higher prevalence of metabolic syndrome (MetS), impaired vascular function, and increased sympathetic activity and are at increased risk of cardiovascular disease. The aim of this study was to assess the effects of 12 weeks of exercise training (70-80% maximum volume of oxygen utilization) in women who had had preeclampsia on physical fitness, components of MetS, vasculature, and autonomic functions compared with healthy control subjects. STUDY DESIGN: Our prospective case-control study included 24 normotensive women who had had preeclampsia and 20 control subjects who were matched for age and postpartum interval (all 6-12 months after delivery). Before and after training, we measured all components of MetS (ie, BP, lipids, glucose/insulin, and albuminuria), carotid intima media thickness (IMT) and brachial and superficial femoral artery endothelial function that used flow-mediated dilation (FMD). Autonomic activity was quantified with power spectral analysis (low-frequency/high-frequency power [LF/HF] ratio). RESULTS: At baseline, women who had had preeclampsia demonstrated higher values of most components of MetS. Compared with the control subjects, women who had had preeclampsia had increased IMT (580 ± 92 µm vs 477 ± 65 µm, respectively), impaired endothelial function (FMD brachial artery, 5.3% ± 2.2% vs 10.8% ± 3.5%, respectively; FMD superficial femoral artery, 4.9% ± 2.1% vs 8.7% ± 3.2%, respectively) and increased LF/HF power ratio (2.2 ± 1.0 vs 1.3 ± 0.4, respectively; all P < .05). In both groups, exercise training decreased values of most components of MetS and IMT, improved FMD, and concurrently reduced LF/HF. Despite these improvements, vascular and autonomic variables did not normalize by 12 weeks of training in women who had had preeclampsia. CONCLUSION: This study demonstrates that exercise training in women who had had preeclampsia and control subjects improves components of MetS, endothelial function, vascular wall thickness, and autonomic control. Nonetheless, trained women who had had preeclampsia only reached a cardiovascular status that is comparable with sedentary healthy control subjects.

Co-occurrence of cardiovascular and prothrombotic risk factors in women with a history of preeclampsia.

OBJECTIVE: Formerly preeclamptic women are at increased risk for remote cardiovascular and thrombotic diseases. We studied co-occurrence of cardiovascular and prothrombotic risk factors within a cohort of formerly preeclamptic women and tested if prevalence of these risk profiles related to onset of preeclampsia in previous pregnancy. METHODS: We evaluated 1,297 nonpregnant formerly preeclamptic women (6-12 months postpartum) for the presence of four risk profiles: circulatory risk profile (hypertension or latent hypertension [low plasma volume, increased vascular resistance, or both]; metabolic syndrome (World Health Organization criteria); thrombophilia (factor V Leiden, prothrombin mutation, or protein C or S deficiency); and hyperhomocysteinemia. Trends between prevalence of these four profiles and onset of preeclampsia were studied using linear regression analysis. RESULTS: After exclusion of 63 women (4.9%) because of incomplete data, 1,234 women were included. One or more risk profiles were detected in 958 of 1,234 (77.6%) formerly preeclamptic women. Circulatory risk profile was more prevalent (66.1%) than hyperhomocysteinemia (18.7%), metabolic syndrome (15.4%), or thrombophilia (10.8%). Prevalence of circulatory risk profile, metabolic syndrome, and hyperhomocysteinemia decreased significantly with gestational age at delivery, whereas thrombophilia did not (P=.22). There was minimal overlap (less than 2%) between metabolic syndrome, thrombophilic profile, and hyperhomocysteinemia. CONCLUSION: Circulatory risk profile is present in two thirds of formerly preeclamptic women. Metabolic syndrome, thrombophilia, and hyperhomocysteinemia are prevalent in 10-20%. There is considerable overlap between circulatory risk profile and other profiles, but not among the three other profiles. Prevalence of these risk factors, except thrombophilia, decreases with gestational age at delivery in preceding pregnancy. LEVEL OF EVIDENCE: : II.

Unexplained first trimester recurrent pregnancy loss and low venous reserves.

BACKGROUND: More than half of recurrent pregnancy loss (RPL) remains unexplained. We hypothesized that women with a history of unexplained RPL (URPL) have low venous reserve. METHODS: Case-control study in 12 women with a history of URPL, 11 healthy nulliparous controls and 12 primiparous controls with a history of uncomplicated pregnancy. To quantify venous reserve, we measured plasma volume (PV, ml/m(2)) and venous compliance in forearm and calf (VC(arm), VC(calf), (ml/dl)/mmHg) during the follicular phase of the menstrual cycle. Mean arterial blood pressure (mmHg) was measured by oscillometry. Arterial demand was evaluated by cardiac index (CI, (l/min)/m(2)). RESULTS: Baseline characteristics were comparable between groups. All groups had similar CI. Women with a history of RPL had 14% and 9% lower mean PV compared with nulliparous and primiparous controls (P < 0.01 and P = 0.04, respectively). In women with URPL, the mean VC(arm) was 25% and 32% lower compared with nulliparous and primiparous controls (P = 0.04 and P < 0.01, respectively), while the mean VC(calf) was 29 and 22% lower compared with the two control groups (P < 0.01 and P = 0.03, respectively). CONCLUSIONS: Women with URPL have lower venous reserves when compared with controls at comparable arterial demand. Interventions that increase venous reserve may improve pregnancy outcome.

Impaired fetal growth and low plasma volume in adult life.

OBJECTIVE: To estimate whether normotensive women who were born small for gestational age have low plasma volume in adult life, which is associated with later chronic hypertension. METHODS: In 280 normotensive women with a history of hypertension in pregnancy, we recorded recalled gestational age and weight at birth and measured plasma volume (I-human serum albumin indicator dilution method). To correct for possible confounders, we recorded recent obstetric history and measured in each individual all constituents of the metabolic syndrome (World Health Organization criteria), sex hormones (progesterone and estradiol), renal function, and cardiac performance at rest (echocardiography). We estimated daily activity level with a validated questionnaire (Short Questionnaire to Assess Health-enhancing physical activity). We studied the relation between women's own birth weight centile and her adult plasma volume (mL) and adjusted for the effects of confounding variables using multiple linear regression analysis. RESULTS: Birth weight correlated positively with adult plasma volume (P<.001). Linear regression analysis demonstrated that each 10 centile change in birth weight is associated with an average change of 46.6 mL (95% confidence interval [CI] 30.8-62.3) in adult plasma volume. This association persisted after adjustment for confounding factors (current body surface area, mean arterial pressure, total vascular resistance, glomerular filtration rate, and a total 24 hours of sodium output). After adjustment, each 10 centile change in birth weight was associated with an average change of 32.1 mL (95% CI 19.6-44.6) in adult plasma volume. Birth centile contributes 14% to the variation in total adult plasma volume. CONCLUSION: Impaired fetal growth is associated with low plasma volume in adult life. LEVEL OF EVIDENCE: II.