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.     

The relation of maternal serum eNOS,NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction

Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels 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.

Patients and methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure >?160/110?mmHg with proteinuria >?5?g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays.

Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed.

Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.     

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective.?The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients.

Patients and methods.?The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay.

Results and conclusions.?Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Umbilical sP-selectin levels are different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus

Objective.?The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies.

Patients and methods. The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria).

Results.?Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008?±?625.703?ng/ml in group P, 275.873?±?174.339?ng/ml in group PI, and 288.719?±?199.039?ng/ml in the control group, respectively.

Conclusions.?Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.     

Estimation of oxidative products of nitric oxide (nitrates, nitrites) in preeclampsia

Oxidative products of nitric oxide, serum nitrates and nitrites were estimated in 50 primigravidas with preeclampsia and in 50 gestation and age-matched normotensive primigravidas. Thirty three (66%) of these women had mild preeclampsia and 17 (34%) had severe preeclampsia. Serum nitrate and nitrite levels were significantly higher in preeclamptic women (nitrates - 15 +/- 1.17; nitrites - 11.82 +/- 1.16 micromol/L) than in the normotensive pregnant women (nitrates 11.82 +/- 1.16; nitrites - 5.08 +/- 0.47 micromol/L, p < 0.001). In preeclamptic women, serum nitrate and nitrite levels correlated with the severity of the disease (mild preeclampsia nitrate - 14.46 +/- 1.98; nitrite 6.21 +/- 0.84 micromol/L, severe preeclampsia nitrate - 16.65 +/- 3.64; Nitrite - 6.87 +/- 1.56 micromol/L). In preeclampsia there was significant positive correlation between nitrate and nitrite levels and diastolic blood pressure and proteinuria.     

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.     

Nitric oxide production with preeclampsia

OBJECTIVE: To clarify production of nitric oxide with pre-eclampsia. METHODS: Production of nitric oxide and elimination of its metabolites, nitrite and nitrate, determines ultimately the level of those metabolites in plasma of subjects whose diets lack them. We measured simultaneously plasma levels and renal clearance of nitrite and nitrate in 20 women with preeclampsia and in 21 healthy pregnant women. Fifteen preeclamptic gravidas were receiving antihypertensive medication and five received betamethasone 1-4 days before the study. Subjects were prescribed low nitrite and nitrate diets for 24 hours and fasted overnight before collection of plasma and urine samples. Nitrite and nitrate were measured spectrophotometrically by Griess reaction. RESULTS: Preeclamptic women had significantly higher plasma levels of nitrite and nitrate (18.1+/-6.2 micromol/L versus 13.0+/-4.3 micromol/L, mean+/-standard deviation [SD], P = .009), which because renal clearance did not differ (0.6+/-0.3 versus 0.7+/-0.3 mL/s), indicated increased production of nitric oxide with preeclampsia that was unaffected by antihypertensives or betamethasone. The mean plasma level of endothelin-1 was increased (5.1+/-1.4 versus 3.6+/-1.0 pg/mL, P < .001), and urinary output of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1alpha was decreased (39.1+/-18.0 versus 61.3+/-35.6 ng/mmol creatinine, P = .019) with preeclampsia. These two endothelial markers showed no relation to plasma nitrite and nitrate. CONCLUSION: Nitric oxide production was increased with preeclampsia. The biologic significance of increased production is unknown, but it might be compensation for the vasoconstriction of preeclampsia.     

Maternal and Umbilical sTNF-R1 in Preeclamptic Pregnancies with Intrauterine Normal and Growth Retarded Fetus

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFα and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

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.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

Plasma and urine beta-thromboglobulin in severe preeclampsia

Summary Beta-thromboglobulin (BTG) has been shown to be a specific platelet protein and can be used as a marker of platelet activation in preeclampsia. Concomitant studies of BTG levels in plasma and urine were performed with eight primiparous severe preeclamptic patients and eight normal primiparous women matched for age. The mean plasma BTG in the severe preeclamptic patients was 186.62±29.93 ng/ml, and in the control group 45.38±31.84 ng/ml. TheP-value for the difference was highly significant (P=0.000). In contrast, the mean urine BTG in the study group was 8.42±4.61 ng/ml, while the mean value for the control group was similar, 5.00±3.20 ng/ml. TheP-value for the difference was not significant (0.05<P<0.10). These results show that urinary BTG cannot be considered an indicator of platelet activation in severe preeclampsia. A low rather express renal impairment. Failure of BTG renal clearance would contribute to further raising the level of plasma BTG.     

REDUCED RED BLOOD CELL DEFORMABILITY,AN INDICATOR FOR HIGH FETAL OR MATERNAL RISK,IS FOUND IN PREECLAMPSIA AND IUGR

Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.     

Discordant clinical presentations of preeclampsia and intrauterine fetal growth restriction with similar pro- and anti-angiogenic profiles

Abstract

Objective: To evaluate the plasma levels of angiogenic factors in preeclampsia (PE) and intrauterine fetal growth restriction (IUGR) and their potential as biomarkers to distinguish normal from pathologic pregnancies.

Methods: Case control study included singleton pregnancies in four categories: (i) normal (n?=?29), (ii) PE (n?=?15), (iii) PE and IUGR (n?=?16) and (iv) IUGR (n?=?24). The classification of IUGR included umbilical artery Doppler resistance. Maternal plasma placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble kinase domain receptor (sKDR) and soluble endoglin (sEng) as well as fetal umbilical artery sFlt-1 levels were determined. Each individual marker and their ratios were assessed for their potential to distinguish normal pregnancy from pregnancies affected by PE and/or IUGR.

Results: We found (i) elevated plasma sFlt-1, sEng and reduced PlGF, sKDR in PE and IUGR; (ii) similar angiogenic profiles in PE and IUGR and (iii) sEng and sFlt-1*sEng/PlGF performed best as biomarkers in identifying pathologic pregnancies.

Conclusions: PE and IUGR have similar angiogenic profiles, suggesting that angiogenic marker profiles lack specificity in identifying PE and that other factors are required for the development of PE instead of IUGR. sEng should be included in a biomarker profile for predicting PE or IUGR.     

Pathological Uterine Perfusion in the Second Trimester Is Not Associated with Neutrophil Activation

Objective: Preeclampsia and intrauterine growth retardation (IUGR) are associated with elevated concentrations of myeloperoxidase (MPO) and polymorphonuclear (PMN) elastase, which indicate maternal neutrophil activation. The aim of the study was to measure maternal MPO and PMN elastase plasma concentrations in second trimester pregnancies with pathological uterine perfusion that are a high risk group for preeclampsia and IUGR, and compare them to normal controls. Methods: The study includes 25 pregnancies with normal and 25 pregnancies with pathological uterine perfusion. In both groups, doppler‐sonographic measurement of uterine perfusion was performed in the twenty‐first week of gestation. Maternal plasma concentrations of MPO and PMN elastase were measured using a specific ELISA for both enzymes. Results: The plasma MPO concentration of pregnant women with normal perfusion did not differ significantly from that of the group with pathological perfusion (27.4 ± 3.3 vs. 23.7 ± 2.0 ng/mL). Likewise, the plasma PMN elastase‐concentration also did not show a significant difference between the groups (5.7 ± 0.5 ng/mL normal vs. 8.0 ± 1.0 ng/mL pathological). Patients with pathological perfusion that later developed preeclampsia or IUGR (9/25) showed unchanged MPO and PMN elastase values in the second trimenon compared to those with pathological perfusion and normal outcome. Conclusions: Pathological uterine perfusion in the second trimester was not associated with maternal neutrophil activation. The measurement of the MPO and PMN elastase concentration suggested that neutrophil activation in preeclampsia or IUGR is a secondary effect of the disease rather than a primary pathophysiological factor.     

Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus.

OBJECTIVE: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients. PATIENTS AND METHODS: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Maternal soluble human leukocyte antigen-G levels in pregnancies complicated by foetal intrauterine growth restriction with and without preeclampsia

ObjectiveThe aim of this study was to investigate the maternal serum of soluble human leukocyte antigen-G (sHLA-G) levels in pregnant women with an isolated intrauterine growth restricted foetus (IUGR) and in preeclamptic pregnancies with and without IUGR.Patients and methodsThe study was conducted on 31 normotensive patients with pregnancy complicated by IUGR, 17 preeclamptic patients with appropriate-for-gestational-age foetal intrauterine growth, 21 with preeclampsia complicated by IUGR, and 32 healthy pregnant controls. Maternal serum sHLA-G levels were calculated using the enzyme-linked immunosorbent assay.ResultsMaternal serum sHLA-G levels tended to be higher in both groups of preeclamptic patients, and were highest in patients with IUGR in the course of severe preeclampsia. Lower serum levels of sHLA-G were observed in the group of normotensive pregnant women with an intrauterine growth restricted foetus, but these differences were not statistically significant. The mean values were 22.759 ± 14.151 units/mL in the IUGR group, 25.948 ± 18.888 units/mL in preeclamptic patients with normal intrauterine foetal growth, 31.646 ± 27.576 units/mL in preeclamptic pregnant women with IUGR, and 24.178 ± 24.828 units/mL in the healthy controls.ConclusionsOur findings suggest that the increased levels of sHLA-G in the maternal serum may play a significant role in the pathogenesis of preeclampsia, especially in preeclampsia complicated by intrauterine foetal growth restriction. These associations may offer a better insight into the etiology and pathogenesis of preeclampsia with and without IUGR. It seems that sHLA-G does not play a clinically significant role in the pathogenesis of isolated intrauterine foetal growth restriction in normotensive pregnancies.     

Comparison of serum and urinary nephrin levels between normal pregnancies and severe preeclampsia

Objective

To compare the levels of urinary excretion of nephrin in women experiencing either normotensive or severe preeclamptic pregnancies, and to examine the relationship between urinary nephrin levels and clinical parameters of preeclampsia.

Study design

In a case control study we collected serum and urine specimens from women with normal pregnancy (n = 30) and from women with severe preeclampsia (n = 43). Serum nephrin levels and urinary nephrin concentrations were measured in all patients.

Results

Both serum and urine concentrations of nephrin were significantly higher in the severe preeclamptic group than in the normal pregnancy group. In addition, we identified a significant relationship between urinary nephrin levels and urine protein concentrations in the severe preeclamptic group. Urine nephrin concentrations were also correlated with serum creatinine levels and with diastolic blood pressure in the severe preeclamptic group.

Conclusion

The positive correlations observed in this study suggest that urinary nephrin excretion might play an important role in the pathogenesis of proteinuria during preeclampsia and could be a good indicator of renal damage.     

Decreasing resistance in the maternal uterine and peripheral arterial system is apparently unrelated to plasma and urinary levels of nitrite/nitrate and cyclic-guanosinmonophosohate during the course of normal pregnancies

AIMS: The aim of the presented study was to clarify the relationship between the pulsatility index of the uterine arteries and the maternal cubital artery and peripheral concentrations of the metabolites of nitric oxide (NO) and its second messenger cyclic guanosinmonophophate (cGMP) during the normal course of pregnancy and postpartum. METHODS: 49 uncomplicated pregnancies were investigated every 4-6 weeks until delivery, 29 of them were additionally investigated postpartum. Paralleling each Doppler sonographic investigation maternal blood and urine samples were taken. The measurements of nitrite/nitrate and cGMP were performed with a colorimetric and radio immuno assay. We demonstrate a significant decrease of the PI of the uterine arteries and of the cubital artery with inverse correlation to advancing gestational age. RESULTS: The concentrations of nitrite/nitrate and cGMP remain stable during gestation and do not correlate to the PI of the uterine and cubital artery. Postpartum a re-increase in the uterine and peripheral resistance can be shown. The concentrations of urinary cGMP and nitrite/nitrate as well as plasma cGMP remain unchanged, whereas plasma nitrite/nitrate decreases postpartum. CONCLUSIONS: The status of NO biosyntheses in normal pregnancy remains controversial. We hypothesize further systemically acting mediators which contribute to the decreasing vascular resistance.     

Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction

BACKGROUND: Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20-30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. METHODS: In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. RESULTS: No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. CONCLUSIONS: We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.     

Homocysteine,folic acid and B12 serum levels in pregnancy complicated with preeclampsia

Objective Elevated plasma homocysteine has been implicated in vascular changes compatible with atherosis and endothelial dysfunction similar to the vascular changes of the placenta in preeclampsia. Previous reports have indicated an increased incidence of hyperohomocysteinemia in preeclamptic patients. The aim of this study was to examine the association of homocysteine levels and preeclampsia in our patients. Study design Prospective study of 28 preeclamptic patients that were matched with 26 normal controls of the same gestational age. Results The preeclamptic group had an increased incidence of cesarean sections (75%), of growth retarded fetuses (50%), intrauterine deaths (7%) and placental abruptions (7%). Mean levels of homocysteine were significantly elevated in the preeclamptic than in control group (11.11 vs. 6.40 μmol/l, P < 0.001). There were no differences between the groups regarding the levels of folic acid (11.12 vs. 9.73 ng/ml, P = 0.55) and vitamin B12 (295.76 vs. 356.15 pg/ml, P = 0.43). Conclusion It is concluded that in our study homocysteine levels are significantly elevated in patients with preeclampsia compared with control group, while no vitamin deficiencies were observed.