Calprotectin, a marker of inflammation, is elevated in the maternal but not in the fetal circulation in preeclampsia

OBJECTIVE: Preeclampsia is associated with excessive inflammatory response compared with normal pregnancy. Calprotectin is an inflammation marker not previously explored in preeclampsia. STUDY DESIGN: Calprotectin in maternal and fetal plasma and amniotic fluid was investigated at cesarean delivery in normal pregnancies and preeclampsia. C-reactive protein (CRP) and plasminogen activator inhibitor type1 (PAI-1) were also analyzed. RESULTS: Maternal median calprotectin, CRP, and PAI-1 concentrations were elevated in preeclampsia (1081 microg/L, 4.8 mg/L, and 51.0 U/mL) compared with control levels (552 microg/L, 3.8 mg/L, and 36.5 U/mL). In the umbilical vein, there were no differences between preeclampsia and controls regarding calprotectin and CRP levels. Maternal calprotectin concentrations correlate with CRP and PAI-1 values for the total study group, but a statistical significant correlation was not found in the preeclamptic group. CONCLUSION: Calprotectin is elevated in the maternal circulation in preeclamptic pregnancies. We found no evidence of inflammatory response in the fetal circulation in preeclampsia.     

Maternal circulating nitrite levels are decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

OBJECTIVE: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. MATERIALS: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks' gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. RESULTS: Maternal circulating nitrite levels in nonpregnant women (1.13 +/- 0.22 microM) were significantly higher than those in the first-trimester pregnant women (0.68 +/- 0.13 microM), second-trimester pregnant women (0.65 +/- 0.13 microM), third-trimester pregnant women (0.48 +/- 0.17 microM), first puerperal week women (0.36 +/- 0.16 microM), and fourth puerperal week women (0.67 +/- 0.17 microM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 +/- 0.17 microM) and third-trimester pregnant women (0.48 +/- 0.17 microM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the groups. CONCLUSION: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.     

Pulse wave reflection in currently and previously preeclamptic women.

OBJECTIVE: Disturbed maternal endothelial function is believed to be central in the pathogenesis of preeclampsia and has been observed to persist for several years following the preeclamptic pregnancy. Endothelial dysfunction has been reported to cause increased pulse wave reflection, a measure of systemic arterial stiffness. This study tested the hypothesis that preeclampsia and a history of preeclampsia are associated with increased pulse wave reflection. DESIGN AND METHODS: We carried out a cross-sectional case-control study of 26 pregnant women with preeclampsia, 26 pregnant controls, 22 normotensive nonpregnant previously preeclamptic women, and 22 nonpregnant controls. Pulse wave reflection was assessed by applanation tonometry on the radial artery. RESULTS: Pregnant preeclamptic women had a significantly higher heart rate-adjusted augmentation index than did pregnant controls (23 +/- 1 vs. 8 +/- 1%, P < 0.001). The augmentation index of women with a history of preeclampsia was similar to that of the nonpregnant controls (9 +/- 2 vs. 9 +/- 2%, P = 0.78). In a multiple linear regression analysis (R2 = 0.76) the augmentation index of pregnant women was independently associated with a diagnosis of preeclampsia (P < 0.001) and heart rate (P < 0.001), but not with mean arterial blood pressure (P = 0.59). CONCLUSIONS: This study demonstrates that pulse wave reflection and, thus, systemic arterial stiffness are increased in pregnant women with preeclampsia, but not in normotensive nonpregnant women with a history of preeclampsia. The results support the concept of generalized vascular dysfunction in preeclampsia.     

Altered thiol status in preeclampsia

Thirty preeclamptic, 30 normotensive pregnant and 25 healthy nonpregnant women were analyzed with regard to the antioxidant system (thiols and superoxide dismutase, SOD). In preeclampsia both plasma and lysate thiol levels were significantly lower compared to controls (p < 0.001). SOD levels were higher in normotensive pregnant women, but were lower in preeclamptic compared to nonpregnant women. This finding of antioxidant changes in the red blood cell suggests that red cell dysfunction is fundamental in the development of preeclampsia, and similar alterations in the balance of the thiol could be present across the endothelial cell membrane.     

Plasma IL-4, IL-8, IL-12, interferon-γ and CRP levels in pregnant women with preeclampsia,and their relation with severity of disease and fetal birth weight

Objective: The aim of the present study was to evaluate the hypothesis that preeclampsia is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses compared with normal pregnancy. We also sought to determine whether there was a correlation between these markers with severity of preeclampsia and fetal birth weight. Methods: The study population consisted of maternal age, gestational age, and body mass index matched 138 pregnant women; 56 normotensive healthy pregnant women (group 1), 42 women with mild preeclampsia (group 2), 40 women with severe preeclampsia (group 3). Results: Plasma interleukin (IL)-8 and C-reactive protein (CRP) levels were significantly higher in group 3 than group 1 (p?<?0.05). Plasma IL-4, IL-12, and interferon (IFN)-γ levels were similar in all groups. Although plasma IL-8 and CRP levels of mild preeclamptic group were higher than control group and lower than severe preeclamptic group, the differences were not statistically significant. There was a positive correlation between IL-12 and fetal birth weight in severe preeclamptic group (p?<?0.05). Conclusions: Elevated maternal serum pro-inflammatory cytokine IL-8 and CRP in severe preeclamptic women compared with normal pregnant women supports the hypothesis that preeclampsia is associated with increased inflammatory responses.     

Plasma thiol status in preeclampsia

OBJECTIVE: To measure plasma thiol levels in women with normal pregnancies, women with preeclampsia, and nonpregnant controls to define plasma thiol's effect on glutathione homeostasis and pathophysiology of preeclampsia. METHODS: Total plasma cysteine, gamma-glutamylcysteine, homocysteine, cysteinylglycine, and glutathione levels were measured in ten nonpregnant women, ten women with normotensive pregnancies, and 20 women with preeclampsia at delivery. RESULTS: Median total plasma levels of all thiols in normotensive pregnant women were significantly lower than in nonpregnant women. Median total plasma cysteine and homocysteine levels in women with preeclampsia were significantly higher compared with pregnant controls (254 versus 190 micromol/L, P < .001; and 13.3 versus 8.4 micromol/L, P < .02, respectively), whereas glutathione levels were significantly lower in women with preeclampsia compared with those in pregnant controls (5.1 versus 6.3 micromol/L, P < .05). CONCLUSION: In women with preeclampsia, homocysteine and cysteine levels, which are lowered in normotensive pregnancy, were comparable to levels in nonpregnant women, whereas glutathione levels were lower. Those results suggest that in women with preeclampsia, glutathione use is higher or its synthesis is disturbed. Therefore, glutathione might affect pathophysiology of preeclampsia.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

The effect of healthy pregnant plasma and preeclamptic plasma on the phagocytosis index of neutrophil granulocytes and monocytes of nonpregnant women

Objective: Phagocyte function of neutrophil granulocytes and monocytes is decreased in healthy pregnancy and further decreased in preeclampsia. The cause of the declined function is unknown. Decreased phagocyte function can lead to the higher infection rate in healthy pregnancy and may also be responsible for the increased susceptibility to infections and high trophoblast concentration in preeclampsia. The aim of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes. Methods: Monocytes and neutrophil granulocytes were separated from the peripheral circulation of six nonpregnant patients and incubated in plasma samples from six healthy pregnant, six preeclamptic pregnant, and six nonpregnant patients. The cells were marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosan molecules. Results: Phagocyte function of neutrophils as well as monocytes from nonpregnant patients were decreased significantly when the cells were incubated in plasma samples from healthy pregnant patients, and further decreased when incubated in plasma samples from preeclamptic pregnant women. Conclusion: The decreased phagocyte function of neutrophil granulocytes and that of monocytes in healthy pregnancy and the further decreased phagocyte function in preeclampsia is caused by factor(s) in the maternal circulation.     

Amniotic fluid and maternal serum leptin levels in pregnant women who subsequently develop preeclampsia

OBJECTIVES: To study the correlation between amniotic fluid leptin levels and maternal serum leptin levels during the early second trimester, and to determine whether the ratios of amniotic fluid leptin levels to maternal serum leptin levels are elevated in pregnant women who subsequently develop preeclampsia. STUDY DESIGN: Samples from 120 pregnant women were included in this prospective study, of which 20 were from pregnant women who subsequently developed preeclampsia and 100 were from normal pregnant women. Both the amniotic fluid and the maternal serum leptin levels were ascertained by radioimmunoassay (RIA). RESULTS: A strong correlation between amniotic fluid leptin levels and maternal serum leptin levels was observed in both preeclamptic and normal pregnant women. In addition, the ratios of amniotic fluid leptin levels to maternal serum leptin levels were positively correlated to amniotic fluid leptin levels, but negatively correlated to maternal serum leptin levels. Furthermore, the ratios of amniotic fluid leptin levels to maternal serum leptin levels in preeclamptic women were significantly higher than those in normal pregnant women. CONCLUSIONS: Amniotic fluid leptin levels correlated with maternal serum leptin levels during the early second trimester. The ratios of amniotic fluid leptin levels to maternal serum leptin levels were elevated in preeclamptic women. However, the maternal serum leptin levels themselves showed no such elevation. Therefore, this elevated ratio may be a marker at the early stage of pregnancy in preeclamptic women.     

Serum soluble Fas levels in preeclampsia

OBJECTIVE: To determine if serum soluble Fas levels are altered in women with preeclampsia. METHODS: Thirty-four pregnant women with preeclampsia and 34 normotensive pregnant women were studied. Subjects were matched as much as possible for demographics. Preeclampsia was defined as proteinuric hypertension. Serum soluble Fas levels were measured by enzyme-linked immunoassay. Two-tailed Student t test, chi(2) test, Pearson correlation coefficients, and analysis of variance with post hoc test were used for statistical analyses. RESULTS: Mean serum soluble Fas levels were significantly higher in preeclamptic than normotensive women (10.59 +/- 0.68 U/mL versus 5.65 +/- 0.35 U/mL, P <.001). CONCLUSION: Elevated serum soluble Fas is associated with preeclampsia. Such elevation might indicate protection of maternal T-lymphocyte apoptosis and consequently lead to the maternal immune intolerance noted in preeclampsia.     

Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia

OBJECTIVE: Soluble CD40 ligand is a transmembrane protein shed from activated platelets that is involved in the activation of endothelial cells. Findings that estradiol (E2) has an inhibitory effect on inflammation and platelet function and that serum E2 levels are low in women with preeclampsia prompted us to investigate the association between soluble CD40 ligand and serum E2 levels in normal pregnancy and in preeclampsia. METHODS: A case-control single-center design was used. The sample included 22 women with severe preeclampsia, 22 matched normotensive pregnant women, and 22 nonpregnant women. Enzyme immunoassay was used to measure soluble CD40 ligand. RESULTS: Significantly higher levels of soluble CD40 ligand were detected in the nonpregnant women (23,767 +/- 15,637 pg/mL) and in the women with preeclampsia (21,025 +/- 45,386 pg/mL) than in the normotensive pregnant women (8,292 +/- 5,926 pg/mL) (P = .026). No significant correlation between soluble CD40 ligand levels and E2 levels was observed. CONCLUSION: The higher levels of soluble CD40 ligand detected in women with preeclampsia may indicate an exaggerated activation of platelets and endothelial cells. LEVEL OF EVIDENCE: II-2.     

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women

Objective: The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. Patients and methods: The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Results: Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2?±?4.3 ng/ml in the IUGR group, 14.1?±?3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1?±?3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6?±?3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Conclusions: Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.     

Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment.

OBJECTIVE: The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity. STUDY DESIGN: Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women. RESULTS: Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05). CONCLUSION: Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.     

Relationship of systemic hemodynamics, left ventricular structure and function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia

OBJECTIVE: This study was done to evaluate left ventricular structure and function among pregnant patients with preeclampsia and compare them with those of normotensive pregnant and nonpregnant subjects. It also tested the hypothesis that abnormalities in left ventricular structure and function are associated with elevated plasma levels of natriuretic peptides. STUDY DESIGN: The study compared 75 pregnant women (n = 40 with preeclampsia; n = 35 normotensive pregnant women) and 10 nonpregnant normotensive control subjects undergoing an echocardiographic and biohumoral (renin activity and aldosterone, atrial natriuretic peptide, and brain natriuretic peptide concentrations) evaluation. The statistical analysis was carried out by analysis of variance, and significance was set at P <.05. RESULTS: Comparison of pregnant patients with preeclampsia versus both normotensive pregnant women and nonpregnant women showed significant increases in left ventricular mass and left ventricular endsystolic and end-diastolic volumes and significant reductions in left ventricular ejection fraction and percentage of fractional shortening. These changes coincided with increases in plasma levels of atrial natriuretic peptide and brain natriuretic peptide that were linearly related to the left ventricular structural and functional changes observed in patients with preeclampsia. CONCLUSION: Pregnant patients with preeclampsia showed adaptation to the increase in systemic blood pressure, with significant modification of left ventricular structure and function related to the plasma levels of both atrial natriuretic peptide and brain natriuretic peptide. A simple evaluation of plasma natriuretic peptide concentrations could help to discriminate patients with preeclampsia who have a condition of mild left ventricular overload.     

Asymmetric dimethylarginine in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women with and without intrauterine growth restriction

Objective.?The aim of this study was to evaluate maternal asymmetric dimethylarginine (ADMA) levels in pregnancies complicated by isolated fetal intrauterine growth restriction (IUGR), in preeclamptic pregnancies with and without IUGR, and in healthy normotensive pregnant women with proper weight fetuses.

Patients and methods.?The study was carried out on 54 normotensive pregnant patients with pregnancy complicated by IUGR, 35 patients with IUGR in the course of preeclampsia, 29 preeclamptic patients with appropriate-for-gestational-age weight infants and 54 healthy normotensive pregnant patients. The ADMA concentrations were evaluated using an ELISA assay.

Results.?The preeclamptic women and normotensive patients with pregnancy complicated by isolated IUGR revealed higher levels of maternal serum ADMA. The mean values of maternal serum ADMA were 0.5730?±?0.1769?μmol/l in the P group, 0.5727?±?0.1756?μmol/l in the PI group, 0.6129?±?0.1517?μmol/l in the IUGR group, and 0.5017?±?0.1116?μmol/l in the control group. The levels of ADMA were additionally higher in the patients with HELLP syndrome and in patients with pregnancy complicated by eclampsia.

Conclusions.?It seems that ADMA is an active agent not only in preeclamptic patients, but also in normotensive pregnant women with isolated fetal IUGR and could be a marker of severity of preeclampsia.     

Serum leptin levels in preeclamptic pregnant women: relationship to thyroid-stimulating hormone, body mass index, and proteinuria

The objective of this study was to evaluate the change in maternal serum leptin levels in preeclampsia and to study the relationship between maternal serum leptin and thyroid-stimulating hormone (TSH), body mass index (BMI), newborn weight, and proteinuria. Eighty-five pregnant women were included in this prospective study, of whom 50 were preeclamptic and 35 were normotensive. Maternal serum leptin levels were measured by the radioimmunoassay technique and TSH levels were measured by the electrochemiluminescence immunoassay method. The maternal serum leptin levels of preeclamptic and normotensive pregnant women were compared. In each group, the relationship between maternal serum leptin levels and TSH levels, BMI, newborn weight, and proteinuria was evaluated. The maternal serum leptin level was significantly higher in the preeclamptics than in the normotensive pregnant women. In the preeclamptic group, there was a strong positive correlation between maternal serum leptin levels and BMI (r =- 0.80; p < 0.001), a very weak positive correlation between maternal serum leptin levels and proteinuria (r = 0.305; p < 0.05), and a very weak inverse correlation between maternal serum leptin levels and birth weight (r = -0.377; p < 0.01). In the same group, there was no correlation between maternal serum leptin and serum TSH levels (r = 0.22; p > 0.05; Pearson correlation test). Leptin may be involved in the pathology of preeclampsia, and elevated maternal serum leptin levels may be a marker for the early stages of preeclampsia in pregnant women.     

Elevated serum concentrations of the angiogenesis inhibitor endostatin in preeclamptic women

OBJECTIVE: Changes in serum levels of angiogenic factors such as vascular endothelial growth factor or placental growth factor were associated with preeclampsia. The aim of our study was to investigate the concentrations of endostatin, a potent endogenous inhibitor of angiogenesis and endothelial or tumor cell growth, in preeclamptic patients. METHODS: Levels of soluble endostatin were determined by enzyme-linked immunosorbent assay and Western blot analysis in sera of nonpregnant women, healthy pregnant women, and patients with different forms of preeclampsia. RESULTS: Statistical analyses of age-matched study groups revealed elevated medians of endostatin concentration for severely (30.5 ng/mL) and mildly (26.05 ng/mL) preeclamptic patients compared with healthy pregnant (17.2 ng/mL) and nonpregnant women (17.2 ng/mL). Western blot analysis confirmed the up-regulation of soluble endostatin molecules (24 kD) in sera of severely preeclamptic patients. CONCLUSION: Elevated concentrations of endostatin could play a role in the pathophysiology of preeclampsia by counteracting the effects of vascular endothelial growth factor. The inhibitor could also be responsible for the observed growth-inhibitory effects of preeclamptic plasma on endothelial cells.     

Renal handling of homocysteine during normal pregnancy and preeclampsia

OBJECTIVE: Maternal plasma homocysteine decreases in normal pregnancy and is significantly increased in preeclampsia. The goal of this study was to investigate the role of the maternal kidney in the changes of plasma homocysteine during normal pregnancy and preeclampsia. METHODS: Plasma and 24-hour urine samples were collected in the same women before, during (first, second, and third trimesters), and after normal pregnancy; and in a separate cross-sectional study of normal pregnant, preeclamptic and nonpregnant women and homocysteine concentrations were measured. RESULTS: Longitudinally, maternal plasma homocysteine decreased significantly by the first trimester compared with prepregnancy and postpartum levels (5.6 +/- 1.8 versus 6.8 +/- 0.5 and 7.4 +/- 0.4 microM, respectively, P<.05 by analysis of variance) and paralleled a significant increase in the renal clearance of homocysteine (2.9 +/- 0.4 versus 1.8 +/- 0.2 and 1.6 +/- 0.2 L/24 hours, respectively, P<.001). In addition, plasma homocysteine was significantly elevated in preeclampsia compared with normal pregnancy (4.4 +/- 0.6 versus 3.2 +/- 0.2 microM, P<.04); however, renal clearance was not different (1.2 +/- 0.1 versus 1.0 +/- 0.1 L/24 hours, P=.55). CONCLUSION: Increases in renal clearance contribute to the decrease in plasma homocysteine during normal pregnancy. However, changes in renal handling do not appear to contribute to the increase in plasma homocysteine in preeclampsia.     

Autonomic Imbalance in Preeclampsia: Evidence for Increased Sympathetic Tone in Response to the Supine-Pressor Test

Objective: To examine whether an increase in sympathetic nervous tone contributes to the augmented response to cardiovascular reflex testing in preeclamptic women.Methods: Maternal electrocardiograms were recorded from 11 nonpregnant women and 25 normotensive and 15 preeclamptic nulliparous women at term, during periods of quiet respiration in the left-lateral position and after shifting to the supine position. Power spectral analysis was applied to epochs of 512 consecutive beat-to-beat intervals to determine the contribution of sympathetic tone, parasympathetic tone, and respiratory sinus arrhythmia to heart rate variability.Results: Both normotensive and preeclamptic pregnant women showed a significant decrease in respiratory sinus arrhythmia and an increase in sympathetic tone compared with nonpregnant women. In nonpregnant and in normotensive pregnant women, shifting from the left-lateral to the supine position did not cause any change in autonomic characteristics. In contrast, preeclamptic women demonstrated a marked increase in power within the very low–frequency range representing sympathetic tone, from 288 ± 214 to 556 ± 322 second²/Hz, in response to the same challenge (P < .05).Conclusion: Third-trimester pregnancy is characterized by sympathetic overactivity. When complicated by preeclampsia, sympathetic overreactivity to cardiovascular reflex testing is observed. Our data support the notion that the pathophysiologic phenomena that characterize preeclampsia are mediated not only by circulating or locally acting vasoactive substances, but also, at least in part, by an increase in sympathetic nervous tone.     

Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia

OBJECTIVES: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity. METHODS: Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked immunoassay. Platelet aggregation was induced by the agonist agents adenosine diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich plasma by aggregometry. RESULTS: Plasma concentrations of active TGF-beta(1) were significantly higher in preeclamptic women (10.41+/-2.07ng/mL) compared with normotensive pregnant women (7.01+/-3.29ng/mL). Platelet number and platelet agonist-induced aggregation percent were significantly lower in patients with preeclampsia than in healthy pregnant women. A significant correlation was observed between TGF-beta(1) plasma levels and platelet agonist-induced aggregation percent as between plasma levels of TGF-beta(1) and platelet number in preeclamptic patients. CONCLUSION: The association between impairment in platelet responsiveness and higher levels of TGF-beta(1) in the plasma of patients with preeclampsia suggests that this cytokine may play a role in the pathophysiological events of preeclampsia that are dependent on platelet activation.