Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.

First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome.

BACKGROUND: Hypertensive disorders, fetal growth restriction and preterm birth are major obstetrical complications and are related to impaired placentation. Early identification of impaired placentation can advance clinical care by preventing or postpone adverse pregnancy outcome. OBJECTIVES: Determine whether sonographic assessed placental vascular development and concomitant changes in inflammation- and/or angiogenesis-related serumproteins differ in the first trimester between uncomplicated pregnancies and pregnancies with adverse outcome. STUDY DESIGN: This prospective longitudinal study defines adverse pregnancy outcome as conditions associated with impaired placentation; fetal growth restriction, hypertensive disorder, preterm birth and placental abruption. The vascularization index, flow index, vascularization flow index and placental volume were determined at 8, 10 and 12 weeks pregnancy from 64 women using 3D power Doppler. Serum levels were analyzed for Angiopoetin-1 and -2, Leptin, VEGF-R, VEGF, and EGF. RESULTS: The vascularization index and vascular flow index increased in uneventful pregnancies with almost 50% between 8 and 12 weeks, resulting in a ∼50% higher vascularization index at 12 weeks compared to women with an adverse pregnancy outcome. Women with an adverse pregnancy outcome (n = 13) had significantly lower indices and placental volumes at all time points measured and these indices did not increase between 8 and 12 weeks. Reduced vascular development was associated with increased Angiopoietin-1 levels at 8 and 12 weeks and increased Leptin levels at 8 weeks. CONCLUSIONS: Pregnancies with an adverse outcome caused by conditions associated with impaired placentation differ from uneventful pregnancies in having reduced placental vascularization accompanied by elevated circulating levels of Angiopoietin-1 and Leptin already in the first trimester.

Circulating Fibronectin and Plasminogen Activator Inhibitor-2 Levels as Possible Predictors of Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIM: Placental syndromes (PS) are characterized by endothelial dysfunction complicating placental dysfunction. Possible markers for endothelial dysfunction and amount of trophoblast are fibronectin and plasminogen activator inhibitor-2 (PAI-2), respectively. We aimed (1) to determine whether in women with recurrent PS (rPS), this complication is preceded by deviating fibronectin- and PAI-2-levels, and (2) whether this is dependent on pre-pregnant plasma volume (PV). METHODS: In 36 former patients, we determined fibronectin- and PAI-2-levels in blood-samples collected preconceptionally and at 12-16 weeks in their next pregnancy. Differences were analyzed between pregnancies with rPS (n = 12) and without rPS (non-rPS, n = 24) using linear mixed models, with subanalyses based on pre-pregnant normal or subnormal PV. RESULTS: We observed higher fibronectin-levels at 12-16 weeks (p < 0.05 and p < 0.01, respectively) and lower PAI-2-levels at 16 weeks (p < 0.01) in the rPS subgroup, the intergroup differences being larger in women with subnormal PV. CONCLUSION: We showed that former PS patients who developed rPS have raised fibronectin- and reduced PAI-2-levels already in early/mid pregnancy. These deviations are even more prominent in women with subnormal pre-pregnant PV, supporting development of a 2-step screening program for former patients to identify the high-risk subgroup of women who may benefit from closer surveillance.

Age-related alterations in cardiac geometry in formerly preeclamptic women and healthy parous controls: an explorative study.

INTRODUCTION: Preeclamptic pregnancies induce concentric left ventricular hypertrophy instead of eccentric left ventricular hypertrophy as seen in healthy pregnancies. Although these differences persist for at least several months postpartum, the long-term fate of these changes is unknown. OBJECTIVE: To explore the age-related changes in cardiovascular structure and function in formerly preeclamptic women relative to parous controls. METHODS: A total of 20 formerly preeclamptic women and 8 parous controls underwent 2 echocardiograms at 1 and 14 years of postpartum. With the nonparametric Mann-Whitney U test and the Wilcoxon Signed Ranks test, we analyzed the between-group differences in cardiac structure and function at both time points and the time-related changes in these indices. RESULTS: Left ventricular geometry and dimensions and systolic function were comparable in the 2 study groups at both time points. The age-related decline in E/A ratio and increase in intraventricular septum thickness were noted in both groups over time, without appreciable differences between groups. CONCLUSION: A history of preeclampsia does not affect the age-related cardiac remodeling over a period of 14 years.

Metabolic syndrome as a risk factor for hypertension after preeclampsia.

OBJECTIVE: To identify metabolic and obstetric risk factors associated with hypertension after preeclampsia. METHODS: We analyzed demographic and clinical data from a postpartum screening (blood pressure, microalbuminuria and fasting plasma levels of glucose, insulin, and lipid profile) from 683 primiparous women with a history of preeclampsia. We excluded women with pre-existing hypertension, kidney disease, or diabetes mellitus. In the group of women who were normotensive at postpartum screening, we evaluated the risk of developing chronic hypertension in the years after screening using questionnaires. RESULTS: Hypertension at postpartum screening (n=107, 17% of all cases) was related to obesity (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.2), elevated fasting levels of insulin (OR 1.7, 95% CI 1.0-2.9), low-density lipoprotein (OR 1.6, 95% CI 1.1-2.6), microalbuminuria (OR 2.3, 95%-CI 1.3-4.0), family history of hypertension (OR 1.8, 95% CI 1.1-2.8), and delivery before 34 weeks of gestation (OR 2.5, 95% CI 1.6-4.0). We identified 27 cases of hypertension within 2,095 person-years during a median 6-year follow-up in the group of women normotensive at postpartum screening. The hazard rate for the development of hypertension was 2.9 (95% CI 1.2-7.5) and 8.1 (95% CI 2.8-22.9), respectively, when two and three or more components of the metabolic syndrome were present; 3.7 (95% CI 1.4-10.0) for family history of hypertension; and 4.3 (95% CI 1.6-11.5) for recurrence of a hypertensive disorder in pregnancy. CONCLUSION: Several metabolic and obstetric risk factors related to hypertension postpartum in the short term and predisposed to the subsequent development of chronic hypertension after preeclampsia in initially normotensive women. LEVEL OF EVIDENCE: III.

Renal function after preeclampsia: a longitudinal pilot study.

BACKGROUND: Women with a history of preeclampsia are at increased risk to develop end-stage renal disease. In this longitudinal study, we evaluated renal function in women with a history of severe preeclampsia and parous controls over a period of 14 years. METHODS: Renal function was measured 1 and then 14 years postpartum by para-aminohippurate and inulin clearances in 20 women with a history of severe preeclampsia and 8 parous controls. RESULTS: The difference in glomerular filtration rate 1 year postpartum between women with a history of preeclampsia and parous controls (112 ± 10 and 125 ± 8 ml/min/1.73 m(2), p < 0.01) had disappeared 14 years postpartum (104 ± 10 and 109 ± 13 ml/min/1.73 m(2), p = 0.37). There was a consistent trend for a lower effective renal plasma flow both 1 and 14 years postpartum (477 ± 90 and 543 ± 92, p = 0.09 and 473 ± 85 and 543 ± 98 ml/min/1.73 m(2), p = 0.07). CONCLUSIONS: This explorative study suggests no accelerated renal function loss in the first decade after preeclampsia.

Platelet monitoring follow-up in a pregnant patient with HELLP syndrome.

Monitoring the course of platelet function in HELLP (haemolysis, elevated liver-enzymes and low platelets) syndrome is important for clinical decision-making. We present a primigravid woman developing HELLP syndrome at 29 weeks and 6 days. Platelet function was monitored by multiple electrode aggregometry (MEA), platelet function analyzer (PFA-100®), platelet count and mean platelet volume (MPV) over an 11-day period. MPV and PFA-100® seem better predictors for platelet function than platelet levels.

Insulin resistance relates to microvascular reactivity 23 years after preeclampsia.

Preeclampsia, an endothelial disorder of pregnancy, is associated with an increased risk on cardiovascular diseases. Cardiovascular risk factors may mediate vascular dysfunction both during pregnancy but also later in life. This study aims to investigate microvascular reactivity, and its relationship with several cardiovascular risk factors, in women with a history of preeclampsia and controls. In this cross-sectional study we compared women with a history of preeclampsia (PE, n=22) with women with uneventful pregnancies only (CON, n=29) 23 years after their first delivery. Participants were matched for BMI, age and date of delivery. We assessed blood concentrations of fasting glucose, HbA1c, insulin, (total, HDL-, LDL-) cholesterol, triglycerides and CRP. Endothelial function was assessed by measurement of skin microcirculatory blood flow by Laser Doppler flowmetry at the dorsal and ventral site of the finger during post-occlusive reactive hyperemia (PORH). PE had higher fasting insulin levels and HOMA-IR compared with CON. The PORH response was similar in both groups. The area under the curve of PORH correlated with insulin and HOMA-IR at both sites, with BMI, triglycerides at the dorsal site and with CRP at the ventral site of the finger in PE and not in CON. In conclusion, 23 years after pregnancy we did not observe a difference in the microvascular hyperemic response between women with a history of preeclampsia and controls. Meanwhile, the results of our study suggest that insulin resistance and other cardiovascular risk factors are related to microvascular reactivity in middle-aged women with a history of preeclampsia.

Reduced renal function after preeclampsia does not result from accelerated age-dependent renal function loss.

Preeclampsia is associated with later kidney disease. This study tested the hypothesis that the normal decline in renal function with age is more rapid in formerly preeclamptic women than in controls. Four groups were compared cross-sectionally: young women with a history of preeclampsia (n = 34), young controls (n = 12), middle-aged women with a history of preeclampsia (n = 22) and middle-aged controls (n = 29). We measured blood pressure (semi-automatic device), effective renal plasma flow (ERPF, para-aminohippurate clearance), glomerular filtration rate (GFR, creatinine clearance) and cardiac output (Doppler echocardiography). ERPF was lower in both young and middle-aged women with a history of preeclampsia relative to controls. The decrease in both GFR and ERPF with age was comparable in both groups. In conclusion, the lower renal function in middle-aged formerly preeclamptic women does not result from accelerated age-dependent renal function loss, but from an already reduced renal function relative to parous controls at young age.

Postpartum reversal of the pregnancy-induced uterine artery remodeling in young, aging, and eNOS-deficient mice.

OBJECTIVES: The progressive rise in uterine blood flow (UBF) during pregnancy is accompanied by outward hypertrophic remodeling of the uterine artery (UA). After birth, UBF falls in concert with the sudden decline in uterine metabolic demands. Arterial remodeling associated with the reversal of increased blood flow has been described in large arteries. It is unclear whether this situation applies to small-sized resistance arteries such as the UA. We investigated the pattern of UA remodeling postpartum in relation to age and endothelial nitric oxide synthase (eNOS) deficiency. METHODS: Uterine artery of 2 and 10 days postpartum young (age 12 weeks), aged (age 40 weeks), and eNOS-deficient (eNOS( -/-), age 12 weeks) mice were dissected and processed for either morphometric analysis (lumen, wall mass) or immunohistochemistry (cellular differentiation, proliferation, and apoptosis). We used data of previously studied control (nonpregnant) and late-pregnant (17 days gestation) mice as reference. RESULTS: By 2 days postpartum, morphometric and cellular characteristics of the UA did not differ from those of late-pregnant UA. By 10 days postpartum, the UA was wider with wall mass being decreased by approximately 30%. Cytological parameters indicated a stable smooth muscle media. Apoptosis was only present in UA of 2 and 10 days pregnant mice. In eNOS(- /-) and aged mice, changes were smaller or absent, respectively. CONCLUSIONS: The outward hypertrophic response of the UA induced by pregnancy regresses gradually postpartum. We speculate that persisting UA widening facilitates UA remodeling in a next pregnancy thereby favoring placentation and with it, allowing for a higher birth weight as usually observed in a second mammalian pregnancy.

Remote hemodynamics and renal function in formerly preeclamptic women.

OBJECTIVE: Women with a history of preeclampsia have an increased risk of developing chronic hypertension and cardiovascular disease. However, little is known about the mechanism responsible for vascular disease in formerly preeclamptic women. The aim of our study was to test whether preeclampsia predisposes to central hemodynamic and renal impairments 20 years after pregnancy. METHODS: In this cross-sectional study, 22 formerly preeclamptic women and 29 parous controls participated, matched for body mass index, age, and date of birth. All women delivered in the period of 1979-1987. Measures included automated blood pressure, Doppler echocardiography, microalbuminuria, paraaminohippurate, and creatinine clearances. Hypertension was defined as blood pressure at or above 140/90 mm Hg, using antihypertensive drugs, or both. RESULTS: Hypertension was present in 55% of the formerly preeclamptic women and 7% of the women in the control group (P<.01). Mean arterial pressure was higher in the formerly preeclamptic women compared with those in the control group (100 and 88 mm Hg, respectively, P<.01). Peripheral vascular resistance was about 20% higher, renal vascular resistance about 30% higher, and renal blood flow about 15% lower in the formerly preeclamptic women compared with those in the control group (P<.05). Similar results were observed after stratification for hypertension in both groups. CONCLUSION: Both normotensive and hypertensive middle-aged, formerly preeclamptic women showed impaired central hemodynamic and renal function compared with parous controls. LEVEL OF EVIDENCE: II.

Simple prepregnant prediction rule for recurrent early-onset hypertensive disease in pregnancy.

OBJECTIVE: We aimed to develop a simple clinically useful prediction rule for early-onset recurrent preeclampsia and/or HELLP syndrome. METHODS: 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. RESULTS: 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. CONCLUSIONS: The prediction rule identified, with clinically relevant predictive capacity, those women at very low risk for recurrent early-onset disease.

Blunted autonomic response to volume expansion in formerly preeclamptic women with low plasma volume.

OBJECTIVE: We hypothesize that low plasma volume in normotensive formerly preeclamptic women reflects reduced venous storage capacity. To test this hypothesis, we compared circulatory and autonomic responses to acute volume loading between women with low and those with normal plasma volume. METHODS: In 24 normotensive formerly preeclamptic women at least 6 months postpartum, we administered 500 mL of iso-oncotic fluid by constant intravenous infusion in 30 minutes, while recording changes in heart rate, blood pressure, cardiac output, and measuring active plasma renin and alpha-atrial natriuretic peptide concentrations. We estimated arterial sympathetic control, cardiac autonomic regulatory balance, and baroreflex sensitivity using spectral analysis. Intergroup and intragroup changes were analyzed nonparametrically. RESULTS: 17 women (71%) had low plasma volume and 7 (29%) had normal plasma volume. Plasma volume expansion induced comparable changes in blood pressure, heart rate, baroreflex sensitivity, and active plasma renin concentration in low plasma volume and normal plasma volume. Cardiac output and alpha-atrial natriuretic peptide increased in low plasma volume but not in normal plasma volume. Volume expansion reduced sympathetic activity ( from 2.41 to 1.76 mm Hg(2), P = .03) in normal plasma volume but not in low plasma volume ( from 2.72 to 2.48 mm Hg(2), P > .05). CONCLUSION: The sympathoinhibitory response to volume expansion is diminished in low plasma volume, which suggests that cardiovascular reflex function is impaired. We speculate that this defect contributes to circulatory maladaptation to pregnancy, sympathetic dominance, and the development of gestational hypertensive disease.

Early-onset preeclampsia and the prevalence of postpartum metabolic syndrome.

OBJECTIVE: To determine the prevalence of the metabolic syndrome postpartum in women with a history of pregnancy complicated by early-onset vascular disorders compared with women with late-onset disorders. METHODS: In this retrospective cohort study 849 women with a history of pregnancy complicated by vascular disorders (preeclampsia; gestational hypertension; hemolysis, elevated liver enzymes, low platelets syndrome; eclampsia; placental abruption; fetal growth restriction; and stillbirth as a result of placental insufficiency) were divided into early-onset (delivery before 32 weeks of gestation, n=376) and late-onset (delivery at or beyond 32 weeks, n=473). By use of four internationally accepted criteria to diagnose metabolic syndrome, we compared its prevalence in both groups using odds ratios (ORs), adjusted for maternal age, smoking, alcohol and coffee consumption, birth weight centile, stillbirth, and interval between delivery and measurements. RESULTS: The metabolic syndrome was present in 15-25% of women after early-onset vascular-complicated pregnancy and in 10-14% of women after late-onset disease, depending on the criteria set used; adjusted OR 2.51 (95% confidence interval [CI] 1.66-3.80) using World Health Organization criteria; adjusted OR 2.01 (95% CI 1.37-2.96) using International Diabetes Federation criteria; adjusted OR 2.16 (95% CI 1.31-3.55) using Third Adult Treatment Panel (ATPIII) criteria; and adjusted OR 2.02 (95% CI 1.28-3.17) using Third Adult Treatment Panel updated criteria. CONCLUSION: The prevalence of the metabolic syndrome postpartum is twice as high in women with a history of early-onset (delivery before 32 weeks) compared to late-onset vascular-complicated pregnancy (delivery at or beyond 32 weeks). LEVEL OF EVIDENCE: II.

Cardiac adaptation to pregnancy in women with a history of preeclampsia and a subnormal plasma volume.

In former preeclamptics, a subnormal plasma volume (LPV) predisposes to hemodynamic maladaptation to pregnancy. Here, we assessed the initial cardiovascular response to pregnancy in LPV (n = 20), in former preeclamptics with normal plasma volume (NPV) (n = 35) and in parous controls (CONTR) (n = 9) by echocardiography, blood pressure and heart rate (HR), before pregnancy, and by 5 and 7 weeks amenorrhea. Data analysis was by nonparametric tests. LPV differed from NPV and CONTR, by a consistently lower E/A ratio (ratio of peak mitral flow velocity in early diastole [E] and that during atrial contraction [A]) and an early-pregnancy rise in left atrial diameter (LAD). Both NPV and LPV differed from CONTR by an early-pregnancy rise in HR. The consistently lower E/A ratio together with the early-pregnancy LAD rise in LPV indicate diastolic dysfunction. The early-pregnancy rise in HR suggests sympathetic dominance in the autonomic control of the circulation.

Orthostatic stress response during the menstrual cycle is unaltered in formerly preeclamptic women with low plasma volume.

Plasma volume (PV) varies with the menstrual cycle not only in healthy parous controls (CON) but also in formerly preeclamptic women with a subnormal PV (LPV). It is unknown whether formerly preeclamptic women with LPV are more susceptible to orthostatic stress than healthy controls. In this study, the authors compared autonomic responses to acute (standing from supine position) and gradual (menstrual cycle) orthostatic stress between LPV and CON. In 11 LPV (PV

Configuration of the microcirculation in pre-eclampsia: possible role of the venular system.

OBJECTIVE: To test the hypothesis that during pre-eclampsia microvascular function and structure are disturbed, which contributes to raised venular resistance. METHODS: The microcirculation of the skin and bulbar conjunctiva was studied in 11 women with preeclampsia and nine parous controls, both in the third trimester and 3 months postpartum. Using intravital videomicroscopy, arteriolar and venular diameters were determined in the conjunctiva. In addition, skin capillary densities and morphology were determined. RESULTS: Conjunctival venular diameters were 30% smaller in pre-eclampsia compared with controls, both during pregnancy (P < 0.01) and postpartum (P = 0.045). Arteriolar diameters also tended to be smaller; however, this difference was not statistically significant. In women with pre-eclampsia we found a higher percentage of tortuous/dilated skin capillaries (5%) compared with controls (0%; P < 0.05). Three months postpartum, this difference had disappeared. Skin capillary densities did not differ between the groups. CONCLUSION: Women with severe pre-eclampsia have narrow venules, both during manifest disease and postpartum. Possibly, these narrow venules raise venular resistance and with it, hydrostatic pressure in the capillary bed. The latter, in turn, may explain the higher number of tortuous/dilated capillaries in women with preeclampsia. These findings support an important role of the venous system in the pathogenesis of pre-eclampsia.

Subclinical signs of vascular damage relate to enhanced platelet responsiveness among nonpregnant formerly preeclamptic women.

OBJECTIVE: In nonpregnant formerly preeclamptic women, the prevalence of occult cardiovascular abnormalities is increased. These high-risk women mildly benefit from low-dose aspirin in the prevention of recurrent disease. How this effect is mediated, either by affecting platelet or vascular function, is still unsettled. In this study, we tested the hypothesis that in these nonpregnant women, enhanced platelet responsiveness is common and related to microvascular damage. STUDY DESIGN: At least 6 months' postpartum we evaluated in 66 formerly preeclamptic women platelet count, volume, and in vitro response to low-dose ADP (0.5 microg/mL). Peripheral levels of fibronectin (microg/mL), von Willebrand factor antigen (%), C-reactive protein (high-sensitive CRP, mg/L), urinary albumin, and protein (24-hour collection, g/mol creatinine) served as markers of vascular damage. Hemodynamic function was determined by plasma volume (iodine I 125 HSA indicator dilution method, mL/kg lean body mass), cardiac index (Doppler, mL/min/m2), blood pressure and heart rate (Dinamap [Critikon, Tampa, FL], mm Hg and beats/min, respectively). Thereafter, we subdivided these 66 women into 2 subgroups either with (n = 10, 15%) or without increased platelet responsiveness (n = 56, 85%). Both groups were compared nonparametrically. RESULTS: Groups were comparable with respect to age, blood pressure, body mass index, parity, plasma volume, and cardiac index. Women with enhanced platelet responsiveness had higher levels of circulation fibronectin and CRP, and displayed more often albuminuria and proteinuria. In addition, even though platelet count was comparable between groups, the mean platelet volume was higher among women with enhanced platelet responsiveness. CONCLUSION: Fifteen percent of formerly preeclamptic women had enhanced platelet responsiveness, which was associated with elevated levels of various markers for (micro) vascular damage. We speculate that in these women platelets are presensitized on a relatively dysfunctional endothelium. Although this association does not prove causality, these results may indicate a subgroup of women who benefit from low-dose aspirin in the prevention of recurrent disease in a next pregnancy.

Low plasma volume coincides with sympathetic hyperactivity and reduced baroreflex sensitivity in formerly preeclamptic patients.

BACKGROUND: Preeclampsia is associated with enhanced sympathetic activity as well as subnormal plasma volume. Meanwhile, in over 50% of these complicated pregnancies, the subnormal plasma volume has been found to persist for a prolonged period after pregnancy. The objective of this study is to test the hypothesis that in normotensive formerly-preeclamptic women, persistence of a subnormal plasma volume coincides with enhanced sympathetic activity and with it, an altered autonomic control of blood pressure. METHODS: Forty-eight formerly-preeclamptic women participated in this study. After measurement of their plasma volume by iodine 125-albumin indicator dilution, they were subdivided into a group with a normal plasma volume (plasma volume > 48 ml/kg lean body mass) and a group with a subnormal plasma volume (< or = 48 ml/kg lean body mass). We performed spectral analysis on their beat-to-beat blood pressure and heart rate recordings and compared both groups using non-parametric tests. RESULTS: Formerly-preeclamptic women with a subnormal plasma volume had a higher sympathetic activity (P = .001) and a lower baroreflex sensitivity (P = .04) than their counterparts with a normal plasma volume. CONCLUSION: In normotensive formerly-preeclamptic women, a subnormal plasma volume coincides with a higher sympathetic activity in the blood pressure regulation and lower baroreflex sensitivity. Whether these alterations in the autonomic control mechanisms are a cause or effect of the subnormal plasma volume remains to be elucidated.