Fibronectin is a Marker for Organ Involvement and may Reflect the Severity of Preeclampsia

Objective. We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia.

Study design. Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester.

Results. In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 ± 0.06 g/L in pregnancy week 16 and 0.43 ±0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 ± 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 ± 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 ± 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 ± 0.22 g/L (p=0.03)].

Conclusion. Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.     

Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation

Objective: We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress. Study Design: Antepartum blood samples were collected ≥6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde. Results: The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P < .04). Similarly, plasma malondialdehyde (P < .001), triglyceride (P < .001), and cellular fibronectin (P < .006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P = .97) or creatinine (P = .28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P = .61), malondialdehyde (P = .32), or triglyceride (P = .89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P < .0001, and r = 0.50, P < .004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P = .03, r = 0.32). Conclusions: Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration. (Am J Obstet Gynecol 1998;179:1605-11.)     

Endothelin Converting Enzyme (ECE) Activity in Normal Pregnancy and Preeclampsia

Objective: Enhanced production of endothelin‐1, due to endothelial cell dysfunction has been considered to be the cause of increased plasma levels of endothelin‐1 in preeclampsia. The present study was aimed at analyzing endothelin‐converting‐enzyme activity, (which reflect the production rate of endothelin‐1 (ET‐1) from big endothelin‐1 (big ET‐1)), big endothelin‐1, and endothelin‐1 concentrations from women with preeclampsia compared to normal pregnant women. Moreover, we analyzed plasma levels of these substances longitudinally throughout normal pregnancy. Study design: Twenty‐nine pregnant healthy women were recruited to the study. Blood samples were obtained at 18, 28, and 38 weeks gestation and six weeks postpartum. Twenty‐seven women with preeclampsia were included. Blood samples were taken at diagnosis (average 35 weeks gestation; range 27–39 weeks) and six weeks postpartum. Endothelin‐1 was analyzed by enzyme linked immunoassay (ELISA) and big‐ET‐1 by radioimmunoassay (RIA). Endothelin‐converting‐enzyme activity was measured using big endothelin‐1 as a substrate and thiorphan as an inhibitor of serum neutral endopeptidase. The amount of endothelin‐1 generated during one hour was measured by RIA. Mean ± SEM is given. Results: In normal pregnancy endothelin‐1 concentrations at 38 weeks and postpartum were increased by 30% (p < 0.01) and 50% (p < 0.001), respectively compared with the second trimester values. Endothelin‐converting‐enzyme activity did not change. At diagnosis endothelin‐1 was higher in women with preeclampsia than in the controls at 38 weeks (0.96 ± 0.07 vs. 0.64 ± 0.06 pmol/L; p < 0.001). Likewise, endothelin‐converting‐enzyme activity was higher in the preeclampsia group (222 ± 15 vs. 172 ± 8 pmol ET/ml/h; p < 0.01). This difference remained at six weeks postpartum. Conclusion: Our findings imply enhanced ET‐1 production in preeclampsia. The elevated endothelin‐converting‐enzyme activity postpartum may indicate an inherent endothelial dysfunction predisposing to preeclampsia or that preeclampsia may cause irreversible changes in endothelial function.     

Plasma markers of endothelial dysfunction in patients with hypertensive disorders of pregnancy: a pilot study in a South Indian population

Objectives: To assess the plasma markers of endothelial dysfunction: VonWillebrand factor (vWF), Platelet derived microparticles (PMPs), and Endothelin-1 (ET-1) in various types of hypertensive disorders of pregnancy and correlate with the pregnancy outcome.

Methods: Plasma levels of vWF, PMPs and ET-1 were analyzed by ELISA kits in gestational hypertension (GH), late onset preeclampsia (LOPE), early onset preeclampsia (EOPE), eclampsia (E) and control pregnant women (CPW) during third trimester. The gestational age at the time of delivery (GA) and birthweight (BW) of the baby also were measured.

Results: The GA and the BW of the baby were found to be significantly lower in EOPE and eclampsia compared to CPW, GH and LOPE. The circulating levels of markers of endothelial dysfunction: vWF, PMPs and ET-1 were significantly higher in EOPE and Eclampsia compared to CPW, GH. Also a negative correlation was observed between vWF levels with pregnancy outcome; GA and BW.

Conclusions: A generalized endothelial dysfunction and poor birth outcomes were observed in hypertensive disorders of pregnancy. There is a spectrum of biochemical derangements related to endothelial dysfunction in GH, EOPE, LOPE and E in that order.     

Higher levels of thyrotropin in pregnancy and adverse pregnancy outcomes

Objective: To determine the frequency of subclinical hypothyroidism in women with pathological pregnancies and the association between elevated thyroid-stimulating hormone (TSH) and pregnancy outcome.

Subjects and methods: A cross-sectional prospective study investigated value of TSH and free thyroxine (FT4) in (1) pregnant women with hypertension (HTA) (N?=?62) or preeclampsia (PE) (N?=?50), (2) women with gestational diabetes mellitus (GDM) (N?=?92) in pregnancy, and (3) women with normal pregnancies (control) (N?=?201). The level of statistical significance was set at p?Results: Of the total 404 respondents, the highest incidence of subclinical hypothyroidism was in the group with preeclampsia 22%, followed HTA group 9.6%; GDM group 10.9% and in the control group 9% (p?p?3?mIU/L (p?=?.003). There were no differences in the average TSH value between GDM (1.93?±?1.03?mIU/L) and control group (p?=?.962).

Conclusions: Early detection and optimal treatment of thyroid dysfunction before and in the first trimester of pregnancy reduces the risk of adverse pregnancy outcomes.     

The maternal plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated in SGA and the magnitude of the increase relates to Doppler abnormalities in the maternal and fetal circulation

Objectives. The soluble form of vascular endothelial growth factor receptor-1 (sVEGFR-1), an antagonist to vascular endothelial growth factor and placental growth factor, has been implicated in the pathophysiology of preeclampsia. Preeclampsia and pregnancy complicated with small for gestational age (SGA) fetuses share some pathophysiologic derangements, such as failure of physiologic transformation of the spiral arteries, endothelial cell dysfunction, and leukocyte activation. The objectives of this study were to: (1) determine whether plasma concentrations of sVEGFR-1 in mothers with SGA fetuses without preeclampsia at the time of diagnosis are different from those in patients with preeclampsia or normal pregnant women, and (2) examine the relationship between plasma concentrations of sVEGFR-1 and Doppler velocimetry in uterine and umbilical arteries in patients with preeclampsia and those with SGA.

Study design. A cross-sectional study was conducted to determine the concentrations of the soluble form of VEGFR-1 in plasma obtained from normal pregnant women (n = 135), women with SGA fetuses (n = 53), and patients with preeclampsia (n = 112). Patients with SGA fetuses and those with preeclampsia were sub-classified according to the results of uterine and umbilical artery Doppler velocimetry examinations. Plasma concentrations of sVEGFR-1 were determined by an ELISA. Since these concentrations change with gestational age, differences among various subgroups were statistically estimated with the delta value, defined as the difference between the observed and expected plasma sVEGFR-1 concentration. The expected values were derived from regression analysis of plasma sVEGFR-1 concentrations in normal pregnancy. Regression analysis and univariate and multivariate analysis were employed.

Results. (1) Mothers with SGA fetuses had a mean plasma concentration of sVEGFR-1 higher than normal pregnant women (p < 0.001), but lower than patients with preeclampsia (p < 0.001). (2) Among patients with SGA fetuses, only those with abnormal uterine artery Doppler velocimetry had a mean plasma sVEGFR-1 concentration significantly higher than normal pregnant women (p < 0.001). (3) Among mothers with SGA fetuses in whom Doppler velocimetry was performed (n = 41), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta of sVEGFR-1 plasma concentration (mean ± standard deviation (SD): 0.69 ± 0.29). Conversely, patients who had normal Doppler velocimetry in both uterine and umbilical arteries had the lowest mean delta (mean ± SD: 0.09 ± 0.29) of sVEGFR-1 plasma concentrations (ANOVA; p < 0.001). (4) Among patients with preeclampsia in whom Doppler velocimetry was performed (n = 69), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta sVEGFR-1 plasma concentration (mean ± SD: 1.01 ± 0.22) among all groups classified (ANOVA; p < 0.001). (5) Among patients with SGA and those with preeclampsia, there was a relationship (Chi-square for trend p < 0.001 for both) between the severity of Doppler velocimetry abnormalities and the proportion of patients who had high delta sVEGFR-1 plasma concentrations (defined as a concentration two standard deviations (2SD) above the mean delta of normal pregnant women). (6) Multiple regression analysis suggested that the diagnostic category (e.g., SGA or preeclampsia), Doppler abnormalities, and gestational age at blood sampling were associated with an increase in plasma sVEGFR-1 concentrations (p < 0.001).

Conclusions. These observations provide support for the participation of the soluble receptor of vascular endothelial growth factor in the pathophysiology of SGA with abnormal uterine artery Doppler velocimetry and preeclampsia. An excess of sVEGFR-1 is released into the maternal circulation of patients with preeclampsia and those with SGA fetuses, as abnormalities of impedance to blood flow involve uterine and umbilical circulation.     

Impairment of thiol-disulfide homeostasis in preeclampsia

Aim: To investigate the effects of severity of preeclampsia on thiol-disulfide homeostasis (TDH).

Material and methods: A total of 108 participants were divided into three groups: Group 1 was composed of pregnant women with no obstetric complications, Group 2 included pregnant women with mild preeclampsia, and Group 3 consisted of pregnant women with severe preeclampsia. TDH parameters were determined, and comparisons of clinical and routine laboratory test findings were made in all groups.

Results: The serum native thiol level was 347.9?±?27.4 in the control group, 237.2?±?44.2 in the mild preeclampsia group, and 227.9?±?53.1 in the severe preeclampsia group (p?<?0.001). The serum total thiol level was 376.1?±?31.9 in the control group, 261.8?±?49.4 in the mild preeclampsia group, and 248.3 ± 57.4 in the severe preeclampsia group (p?<?0.001). The disulfide level was 14.1?±?5.6 in the control group, 12.3?±?5.1 in the mild preeclampsia group, and 10.2?±?4.8 in the severe preeclampsia group (p?=?0.001). A significant correlation between impairment in degree of TDH and severity of preeclampsia was observed.

Conclusion: TDH was impaired in women with preeclampsia, and this impairment increased with disease severity. Therefore, impaired TDH may have a role in the etiopathogenesis of the disease.     

Incidence of superimposed preeclampsia among pregnant Asian women with chronic hypertension

Objective: To determine the incidence and associated factors of superimposed preeclampsia among pregnant women with chronic hypertension.

Methods: A total of 300 pregnant women diagnosed with chronic hypertension were reviewed. Data were retrieved from medical records, including obstetric data, characteristics of hypertension, and pregnancy outcomes. Incidence of superimposed preeclampsia was estimated. Various characteristics were compared to determine associated risk factors.

Results: Mean age of the cohort was 34.3 years, 47% were nulliparous, 50% had hypertension before pregnancy, and the others presented with hypertension before 20 weeks. Incidence of superimposed preeclampsia was 43.3% (95% confidence interval (CI) 37.8–48.9). Women with superimposed preeclampsia were significantly more likely to have mean arterial pressure (MAP) ≥105 mmHg at 18–20 and 24–28 weeks. Adverse neonatal outcomes were significantly more common among women with superimposed preeclampsia, including small for gestational age, low birth weight, asphyxia, and neonatal intensive care unit admission. Logistic regression analysis demonstrated that only MAP ≥105 mmHg at 24–28 weeks was independently associated with the increased risk of superimposed preeclampsia by 1.8-fold (adjusted OR 1.8, 95% CI 1.1–3.1, p = 0.031).

Conclusion: Incidence of superimposed preeclampsia was 43.3% among pregnant women with chronic hypertension, with increased adverse neonatal outcomes. High MAP ≥105 mmHg during late second trimester might be an important predictor of the condition.     

Serum homocysteine levels in pregnant women with preeclampsia

Preeclampsia is one of the most common and severe pregnancy complications, which ethiology remains unclear. It is certain that endothelial dysfunction plays a key role in the development of preeclampsia. Homocysteine is an important independent cardiovascular risk factor, which might induce the endothelial dysfunction observed in preeclampsia. 26 pregnant women--14 with preeclampsia (group 1) and 12 healthy term pregnant controls (group 2) were enrolled in the study between December 2003 and August 2004. Six of the women in this group had a superimposed preeclampsia. The mean homocysteine level in the first group was 11,04 mol/l, while in the control group it was 6,24 micromol/l (p < 0.05). The women with a severe preeclampsia had a significantly higher serum homocysteine levels than those with mild form (F = 0.025). Seven of the patients (50%) gave birth before 34th weeks of gestation. The study finds a link between the serum homocysteine as an endothelial dysfunction marker and the development of preeclampsia and a relation between the severity of preeclampsia and the degree of the elevation of the serum homocysteine levels.     

SERUM ANTIBODIES TO OXIDIZED LOW-DENSITY LIPOPROTEIN IN PREGNANT WOMEN WITH PREECLAMPSIA AND CHRONIC HYPERTENSION: LACK OF CORRELATION WITH LIPID PEROXIDES

Objectives: To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension.

Methods: Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension.

Results: Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women.

Conclusions: Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels.     

PRORENIN CONCENTRATION IN THE HYPERTENSIVE DISORDERS IN PREGNANCY

Objective: To evaluate the plasma prorenin levels during the three trimesters of normal pregnancy, their prognostic value, and their correlation with hypertensive disorders of pregnancy.

Design: A prospective study in which plasma prorenin and renin levels were measured in 55 healthy pregnant women and 66 who developed gestational hypertension or preeclampsia. The patients were classified as mild preeclampsia (mild PE), severe preeclampsia (severe PE), chronic hypertension and superimposed preeclampsia upon chronic hypertension (superimposed PE).

Method: Venous blood samples were collected in the first, second and third trimesters and during delivery or cesarean. Plasma renin concentration (PRC) was measured by radioinmmunoassay before and after incubation with trypsin solution. The difference gave plasma prorenin concentration (PProRC).

Results: PRC and PProRC were significantly higher in pregnant women compared with healthy non-pregnant. PRC was significantly increased in the first trimester in the chronic hypertension group and a lower value was found in the first trimester in the superimposed PE compared with those in healthy pregnant women. No differences in other groups were found. PProRC showed a significant lower value in the first and third trimesters in the severe PE group. In the superimposed PE a low value of PProRC similar to those of non-pregnant women was found.

Conclusions: The results show that the different types of hypertension in pregnancy have different profiles of PProRC and PRC in relation to development of preeclampsia. The absence of increase of PProRC in the first trimester of superimposed PE may have a prognostic value.     

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.     

Hypertriglyceridemia Is Linked to Reduced Nitric Oxide Synthesis in Women with Hypertensive Disorders of Pregnancy

Background: Hypertensive disorders of pregnancy (HDP), which affect 8% to 15% of pregnancies, are associated with nitric oxide dysfunction and hyperlipidemia, but their precise role in HDP remains controversial. In order to gain more insight into the mechanisms underlying HDP, we evaluated some indicators common to the diseases associated with endothelial dysfunction. Methods: Plasma samples were obtained from 47 normotensive women (control group) and from 27 women with HDP (experimental group). All women were 7 months pregnant. Body mass index as well as triglycerides, nitrite concentrations, total cholesterol, LDL-cholesterol, HDL-cholesterol, glucose, and glycated hemoglobin were determined. Results: Our results showed significant differences in body mass index (30.4 ± 1.3 vs 28.3 ± 0.6 kg/m², p < 0.05), triglycerides (363 ± 137 vs. 263 ± 80 mg/dL, p < 0.01), nitrites (19.6 ± 5.2 vs. 15.2 ± 5.0 μmol/L, p < 0.01), and glucose (92 ± 25 vs. 81 ± 10.8 mg/dL, p < 0.05) in women from the experimental group compared with the control group. Interestingly, nitric oxide synthesis was significantly reduced when triglycerides and cholesterol concentrations were increased (p < 0.018 and p < 0.002, respectively). Moreover, there was a strong association (odds ratio, 3.5) between a family history of type 2 diabetes mellitus and the development of HDP, especially preeclampsia. Conclusions: It may be useful to screen pregnant women for plasma nitrites and serum triglycerides to identify those at risk of developing HDP, especially in women with a family history of type 2 diabetes mellitus.     

Plasma Factors that Determine Endothelial Cell Lipid Toxicity in Vitro Correctly Identify Women with Preeclampsia in Early and Late Pregnancy

Objective: We proposed that women who develop preeclampsia have a low ratio of “protective” toxicity preventing activity (TxPA) to “toxic” very low density lipoproteins (VLDL) late in pregnancy. Having confirmed this hypothesis, we then tested whether this low ratio would manifest itself early in the pregnancy of women who develop preeclampsia.

Methods: Serially collected plasma from women who developed preeclampsia and from matched controls was assayed blind for TxPA, tri-glycerides, cholesterol, high-density lipoproteins, albumin, and nonesterified fatty acids (NEFA).

Main Outcome Measures: Plasma concentrations of lipids, NEFA, and proteins which bind NEFA (TxPA and albumin) were measured in normal and preeclamptic women. These parameters were formulated prior to data collection because of the low albumin/triglyceride ratios and the elevated NEFA levels reported to occur in preeclampsia.

Results: In late pregnancy, TxPA was lower (1.82 ± 0.63 vs. 2.30 ± 0.40 g/dL, P = 0.008) and VLDL higher (292 ± 130 vs. 206 ± 60 mg/dL, P = 0.013) in preeclamptics than in controls. Discrimination analysis (TxPA and triglyceride), correctly classified 95% of the preeclamptics and 79% of the controls in late pregnancy. The ratio of TxPA to non-TxPA and triglyceride correctly classified 92% of the preeclamptics and 85% of the controls in early pregnancy.

Conclusions: The ratio of TxPA to VLDL accurately distinguishes preeclamptic from normal pregnant women, suggesting that both these factors are involved in the development of preeclampsia.     

Serum Levels of Alpha-Tocopherol in Hypertensive Pregnancies

Objective: Assess alpha-tocopherol serum levels in a population of pregnant women affected by different hypertensive disorders.

Methods: Alpha-tocopherol serum levels were determined by high-pressure liquid chromatography in 177 third-trimester pregnant women: 63 affected by gestational hypertension, 69 by preeclampsia, 26 by chronic hypertension, and 19 normotensive controls. In 39 out of the 158 hypertensive patients, pregnancy was complicated by intrauterine growth retardation (IUGR).

Results: Alpha-tocopherol serum levels did not show any significant difference among gestational hypertensive, preeclamptic, chronic hypertensive patients, and controls. A significant reduction of alpha-tocopherol levels was observed when we compared patients with IUGR and patients with a normally grown fetus. Such significant reduction was maintained when we analyzed the different classes of hypertension.

Conclusions: The reduction of antioxidant nutrients and, in particular, of alpha-tocopherol is not a feature of preeclampsia and seems better correlated with the presence of placental insufficiency, rather than maternal disease.     

Validation and Compliance of a Home Monitoring Device in Pregnancy: Microlife WatchBP Home

Objective. To assess the accuracy and patient compliance in using a novel home blood pressure monitoring device in high-risk pregnancy. Methods. Device accuracy was assessed according to the British Hypertension Society protocol in 45 pregnant women, including 15 with preeclampsia. Twenty-one high-risk pregnant women used the device in addition to their antenatal care. Results. The device achieved a mean difference ± SD of 0.4 ± 7.3/?0.4 ± 5.5 mmHg (pregnancy) and ?2.6 ± 7.0/0.8 ± 4.4 mmHg (preeclampsia) for systolic/diastolic pressure. Eighty-one percent of women did at least 6 measurements/day and all women did at least 2 measurements/week. Conclusion. The Microlife WatchBP Home is accurate for use in pregnancy and increases surveillance in compliant patients.     

LONG-TERM PROGNOSIS OF HYPERTENSION IN PREGNANCY

Objectives To assess the prevalence of subsequent hypertension in women with hypertensive pregnancies and evaluate it according to the subclassifications of hypertension in pregnancy.

Methods A survey was carried out in 476 women with hypertensive pregnancies (cases) and 226 normotensive controls delivered between 1973 and 1991 in a tertiary-level teaching hospital. They were invited to participate by mail and 273 cases (57%) and 86 controls (38%) completed the analysis. Outcomes assessed were prevalences of hypertension, diabetes, and hypercholesterolemia, together with cardiovascular morbidity.

Results Among responders, age and parity were similar in both groups although follow-up time was longer in controls. Subsequent hypertension was more frequent within cases. After excluding chronic and unclassifiable hypertension, the mean blood pressure was higher in all other forms of pregnancy hypertension (103 ± 13 mm Hg versus 94 ± 13 mm Hg, p < 0.001); long-term hypertension prevalence was 45% in cases and 14% in controls [odds ratio (OR) = 5.1; 95% confidence interval (95% CI) = 2.5–9.8; p < 0.001]. There were no differences with respect to the prevalences of subsequent diabetes or hypercholesterolemia. Remote hypertension was more common following gestational hypertension (54%) than in preeclampsia (38%), eclampsia (14%), or normotensive cases (14%) (OR for gestational hypertension versus normotensives = 7.2; 95% CI = 3.4–14.8, p < 0.001, and OR for preeclampsia versus normotensives = 3.7; 95% CI = 1.7–7.9, p < 0.001).

Conclusions After an average of 13.6 years since the index pregnancy, women with hypertensive pregnancies have an increased risk of subsequent hypertension. Gestational hypertension is the hypertensive disorder of pregnancy with the highest incidence of subsequent hypertension. Women with preeclampsia have a greater tendency to develop hypertension than women with normotensive pregnancies. By contrast, women with eclampsia do not.

     

Maternal levels of vitamin E in normal and preeclamptic pregnancy

Vitamin E, a potent antioxidant, may play a role in preventing preeclampsia. Maternal blood samples were collected between 28 and 40 weeks’ gestation from women with mild preeclampsia (n=17), women with severe preeclampsia (n=16) and the control group (n=15). This control group was consisted of 15 pregnant women without hypertension episode during their pregnancy. Vitamin E levels were significantly higher in normotensive pregnant women (1.00±0.20 mg/dL) than in those with mild (0.56±0.15 mg/dL) or severe (0.37±0.75 mg/dL) preeclampsia (P<0.001). In preeclamptic women, when systolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05), also when diastolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05). Measurement of vitamin E concentration in plasma may be useful as a prognostic marker of the likely development of preeclampsia. Received: May 1999 / Accepted: 7 December 1999     

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.     

Effects of Serum from Preeclamptic Women on Prostacyclin Production by Human Endothelial Cells

There is growing evidence that proteinuric hypertension of pregnancy (preeclampsia) is associated with endothelial dysfunction. The aim of this study was to evaluate the effects of serum from preeclamptic patients on basal and agonist-stimulated prostacyclin production by human umbilical vein endothelial cells (HUVEC) in culture and to compare these to the effects of serum from normal pregnant and nonpregnant women. During a 24 h incubation of HUVEC with 20% preeclampsia serum, baseline prostacyclin output was significantly (P < 0.01) increased over the control groups. However, this response was attenuated by extending the exposure to 72 h. Histamine, thrombin and the calcium ionophore, A23187, all acutely increased prostacyclin production, but the increase relative to baseline levels was greatest in HUVEC preincubated for 24 h in normal serum and was smallest when cells were preincubated in preeclampsia serum. We conclude that 1) preeclampsia serum transiently promotes prostacyclin production in HUVEC derived from normal pregnancies, and 2) the relative increase in response to agonists is reduced by preeclampsia serum, compared to normal pregnancy sera.