Changes in Maternal Serum Thioredoxin (TRX) Levels after Delivery in Preeclamptic and Normotensive Pregnant Women

Objective. To investigate changes of maternal plasma thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. Methods. Ten normotensive women (group A) were compared to 17 women with severe preeclampsia (group B). TRX levels were assessed in maternal plasma, immediately after delivery and 12–16 weeks postpartum. Results. There were no differences in plasma TRX levels between the two groups immediately antepartum (p = 0.095). A significant reduction in plasma TRX levels was found immediately following delivery only in normotensive group (117.76 ± 37.19 ng/mL vs. 43.45 ± 21.11 ng/mL, p = 0.002), but not in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 53.82 ± 44.34 ng/mL, p = 0.12). Plasma TRX levels remained unchanged in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 55.37 ± 52.23 ng/mL, p = 0.2) at 12–14 weeks postpartum.     

Increased plasma soluble fms-like tyrosine kinase 1 and endoglin levels in pregnancies complicated with preeclampsia

Background.?Increased maternal plasma levels of proinflammatory cytokines as well as the anti-angiogenic agents soluble fms-like tyrosine kinase 1 (sFlt-1) and endoglin (sEng) are associated with promoting vascular dysfunction leading to the maternal syndrome of preeclampsia.

Objective and method.?Nulliparous women complicated with preeclampsia (n = 29) and their corresponding controls (n = 29) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil-Ecuador were requested to participate in a study evaluating plasma levels of soluble anti-angiogenic factors (sFlt-1 and sEng) and pro-inflammatory cytokines: interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α). Maternal and neonatal data were also assessed and compared among the study groups.

Results.?No significant differences in either maternal baseline or delivery characteristics were observed among the study groups. Compared with controls, preeclamptic women exhibited higher plasma levels of sFlt-1 (19.0 ± 15.1 vs. 12 ± 8.3 ng/mL) and of sEng (20.4 ± 9.9 vs.15.9 ± 9.4 ng/mL); respectively, p < 0.05. Women with severe disease displayed higher sFlt-1 and sEng levels when compared with mild ones (34.5 ± 11.6 vs. 9.5 ± 1.6 ng/mL, and 29.5 ± 9.0 vs. 14.8. ± 5.2 ng/mL, respectively; p < 0.001). In contrast, women with preeclampsia exhibited significant lower IL-8 and G-CSF levels compared with controls. No differences existed between either group in IL-6 levels or TNF-α.

Conclusion.?Consistent with previous reports, increased sFlt-1 and Eng levels in maternal plasma is consistent with vascular dysfunction found in gestations complicated with preeclampsia.     

HEAT SHOCK PROTEIN 70 IS NOT INCREASED IN WOMEN WITH SEVERE PREECLAMPSIA

Objective: The purpose of this study is to determine if heat shock protein 70 (Hsp 70), a marker of cellular stress, is elevated in pregnancies complicated by severe preeclampsia. Methods: Maternal blood was collected from women with severe preeclampsia (n=47) matched for delivery gestational age to normotensive pregnant controls (n=51). Hsp 70 concentrations were measured by standard ELISA techniques. Data were analyzed with the Student's t-test and chi-square test. Main outcome measures: The primary outcome measured was Hsp 70 concentrations. Our hypothesis prior to data collection was that HSP 70 would be increased in women with severe preeclampsia. Results: Compared with normotensive women, those with severe preeclampsia had similar maternal age, parity, delivery gestational age, maternal weight, and ethnicity. There was no difference in mean concentrations of Hsp 70 between women with severe preeclampsia and controls (35.4±96.7 vs. 30.1±11.5, p=0.80). Similar numbers of women with severe preeclampsia (n=28) and controls (n=30) had Hsp 70 concentrations below the 0.02 ng/dL level of detection (chi-square value=0.024, p=0.88). Conclusion: Hsp 70 concentrations are not elevated in women with severe preeclampsia.     

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     

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.     

Differential regulation of TNF receptors in maternal leukocytes is associated with severe preterm preeclampsia

We tested the hypothesis that maternal peripheral blood leukocytes contribute to elevated levels of soluble TNF receptors (sTNFR) in preeclampsia (PE) with concomitant intrauterine growth restriction (IUGR). TNFR1 and TNFR2 were evaluated in a cross-sectional study comparing preeclamptic (n?=?15) with or without IUGR versus normotensive pregnant women (PREG, n?=?30), and non-pregnant controls (Con; n?=?20). Plasma levels of sTNFR1 were higher in PE (1675.0?±?227.1?pg/mL) compared with PREG (1035.0?±?101.1?pg/mL) and Con (589.3?±?82.67?pg/mL), with the highest values observed in PE with IUGR (2624.0?±?421.4?pg/mL; n?=?6). Plasma sTNFR2 was higher during pregnancy (PE: 1836.0?±?198.7?pg/mL; PREG: 1697.0?±?95.0?pg/mL) compared with Con (598.3?±?82.7?pg/mL). Urinary levels of sTNFR1 and sTNFR2 were higher in PE and PREG compared with the Con group. Abundance of TNFR1 mRNA in peripheral blood leukocytes was strongly correlated with plasma levels of sTNFR1 in PE. However, TNFR2 mRNA accumulation in leukocytes did not correlate with sTNFR2 plasma levels. The level of sTNFR1 in plasma was correlated with body weight of the newborn (r?=??0.56). The data suggest that maternal leukocytes contribute to sTNFR1 levels in plasma in association with decreasing newborn weight and PE with concomitant IUGR.     

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.     

Homocysteine and Cellular Fibronectin are Increased in Preeclampsia,not Transient Hypertension of Pregnancy

Objective. The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction.

Methods. We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls.

Results. Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9±14.1 μg/mL versus 10.9±5.4 and 10.1±6.2 μg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3±2.5 μM versus 5.5±2.2 and 5.4±3.4 μM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine.

Conclusions. The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.     

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.     

Maternal serum apelin and YKL-40 levels in early and late-onset pre-eclampsia

Objective: The aim of the present study is to investigate whether alterations in the serum levels of apelin and YKL-40 differ between early and late onset pre-eclampsia and whether there is a correlation between apelin and YKL-40 in women who subsequently develop early and late pre-eclampsia. Materials and methods: A total number of 80 pregnant women, 40 with normal pregnancy and 40 with pre-eclampsia, were included in the present study. Both the normal pregnant and pre-eclamptic subjects were subdivided into two groups. Serum YKL-40 and apelin concentrations were measured. Results: Mean maternal serum YKL-40 levels were both lower in women who subsequently developed early (87.45?±?3.07 versus 103.40?±?4.29) or late (96.43?±?4.06 versus 99.87?±?3.63) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p?p?>?0.05). Mean maternal serum apelin levels were both higher in women who subsequently developed early (8.6?±?3.6 versus 5.7?±?1.2) or late (9.6?±?2.5 versus 8.1?±?1.8) pre-eclampsia than those who remained normotensive. The difference was significant in early-onset preeclamptic women (p?p?>?0.05). There was a significant negative correlation between serum apelin and YKL-40 levels (r?=??0.48, p?=?0.001). Conclusion: Circulating levels of apelin are significantly increased in early-onset pre-eclampsia, indicating the role of apelin in the discrimination of the early-onset of pre-eclampsia. On the other hand, maternal serum YKL-40 levels are not elavated significantly, indicating that adipose-derived apelin is primarily involved in the vascular pathogenesis of early-onset pre-eclampsia than macrophage-derived YKL-40.     

Maternal serum autotaxin levels in early- and late-onset preeclampsia

Purpose: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital.

Methods: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients.

Results: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels.

Conclusion: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.     

MATRIX METALLOPROTEINASE-2 IS ELEVATED IN THE PLASMA OF WOMEN WITH PREECLAMPSIA

Objective: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2) alters vascular function through cleavage of vasoactive peptides, resulting in increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized that MMP levels are increased in women with preeclampsia. In addition, because vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of preeclampsia and is involved in angiogenesis that requires the release of proteases to allow for migration of endothelial cells, we hypothesized that VEGF increases release of MMPs from endothelial cells.

Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human umbilical vein endothelial cells in response to VEGF (0.1–10 ng/mL).

Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancies (arbitrary intensity units: 690 ±111 and 252 ±56, respectively, p<0.05). MMP-9 levels were below the level of detection. In addition, VEGF stimulated endothelial MMP-2 and MMP-9 release in a concentration- and time-dependent (6–24 h) manner. Moreover, VEGF stimulation of MMP release occurs without significantly affecting the release of TIMP-1 and TIMP-2.

Conclusions: These data suggest that VEGF promotes secretion of MMPs from endothelial cells that, in turn, could alter vascular function in women with preeclampsia.     

Angiopoietin-2: A Promising Indicator for the Occurrence of Severe Preeclampsia

Background. The known connection between placental hypoxia and the development of preeclampsia suggests that angiogenic factors in the placenta would be changed and affect the maternal and/or umbilical cord plasma levels in patients with preeclampsia. Objective. The aim of this study was to determine the difference and correlation of placental mRNA expression and maternal/umbilical cord plasma concentrations of vascular endothelial growth factor A (VEGF-A), angiopoietin-1, and angiopoietin-2 between women with severe preeclampsia and normal pregnancies. Methods. Sixteen patients with severe preeclampsia and 29 normotensive pregnant women were studied. The placental mRNA expression was assessed using real-time quantitative RT-PCR analysis. Maternal/umbilical cord plasma levels were measured using an enzyme-linked immunoassay. Nonparametric methods were applied for statistical analysis. Results. Placental mRNA expression of angiopoietin-2 was significantly increased in patients with severe preeclampsia (p < 0.001). The maternal plasma angiopoietin-2 protein level was also significantly increased in women with severe preeclampsia (p < 0.05) and showed a positive correlation with the placental mRNA expression of angiopoietin-2 (r = 0.54, p < 0.005). For VEGF-A and angiopoietin-1, there were no significant differences between the two groups. A maternal plasma angiopoietin-2 concentration of 8.4 ng/mL had a sensitivity of 63% and a specificity of 83% for predicting severe preeclampsia. Conclusion. Placental angiopoietin-2 mRNA expression was increased and correlated with the maternal plasma angiopoietin-2 protein concentration in women with severe preeclampsia. This suggests that the plasma angiopoietin-2 protein level may be a candidate marker for severe preeclampsia.     

Vitamin D deficiency and placental calcification in low-risk obstetric population: are they related?

Objective: We aimed to evaluate the relationship between placental calcification and maternal and cord blood 25-hydroxyvitamin-D₃ [25(OH)D] and calcium concentrations in low-risk obstetric population at term and their consequences.

Methods: Sixty non-complicated pregnant women at term admitted to maternity clinic were included in this prospective case-control study and classified into one of two groups according to grade of placental calcification by defined the Grannum classification: Group 1 (n=30), with Grade 3 placenta and Group 2 (n=30), the control group, no placental calcification noted. Baseline characteristics, maternal serum and umbilical cord 25(OH)D and calcium levels were compared between groups.

Results: The mean age of subjects was 26.4?±?5.7 years. The mean serum 25(OH)D concentration of women (n=60) was 9.3?±?3.4 (range 5.59–15.48) ng/mL. The prevalence of vitamin D deficiency [25(OH)D?<20 ng/mL] was 100%. Maternal serum and cord blood calcium levels were significantly higher in Group 1 (p=0.036; p=0.037, respectively). In Group 2, maternal serum and cord blood 25(OH)D levels were higher than Group 1 (11.35?±?6.54 and 10.22?±?3.59 versus 9.6?±?4.2 and 9.07?±?2.43 ng/mL); but the difference is not statistically significant.

Conclusions: Higher maternal calcium and lower 25(OH)D levels detected in patients with Grade 3 placental calcification indicated the importance of placenta on vitamin D regulation.     

Preeclampsia is associated with an elevation of plasma sMet concentrations in the second trimester

Abstract

Objective: The aim of this study was to investigate the association between anti-angiogenic factor soluble c-Met (sMet) concentrations in maternal plasma and the risk of preeclampsia.

Methods: The pregnant women included in this study (1) had subsequent preeclampsia (n?=?52) and were compared to normal controls (n?=?104) at the time of amniocentesis (15–20 weeks); and (2) had preeclampsia (n?=?63) and were compared to normal controls (n?=?112) at the time of diagnosis of preeclampsia (29–40 weeks). sMet concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results: Maternal plasma sMet concentrations were significantly higher in both women with subsequent preeclampsia (median: 1372.7?ng/ml versus 1100.5?ng/ml; p?=?0.036) and women with preeclampsia (median: 1651.9?ng/ml versus 1364.7?ng/ml; p?<?0.001) than in the controls. After adjusting for potential confounding factors, the risks of developing preeclampsia were as follows: adjusted odds ratio 2.5 (95% confidence interval, 1.2–5.2; p?=?0.016) for second trimester sMet concentration with a cut-off value of 1223.5?ng/ml and 4.4 (95% confidence interval, 2.2–9.1; p?<?0.001) for third trimester sMet concentration with a cut-off value of 1460.3?ng/ml.

Conclusion: Elevated maternal plasma sMet concentrations were independently associated with the increased risk of preeclampsia.     

Levels of antibodies against protein C and protein S in pregnancy and in preeclampsia

Objectives.?The clinical relevance of antibodies anti-protein C and anti-protein S in pregnancy remains controversial. We evaluate whether, in the absence of thrombophilic diseases, maternal plasma levels of antibodies (IgM and IgG) change during pregnancy and in preeclampsia (PE), with and without superimposed fetal growth restriction (FGR).

Methods.?A retrospective cohort of 50 women with PE (n = 30) and PE + FGR (n = 20) and 70 controls [first trimester (n = 20); second trimester (n = 20); third trimester (n = 30)] were enrolled in the study.

Results.?In healthy pregnant women, plasma levels of anti-protein C antibodies decreased from first to third trimester and were below the range of positivity. IgM anti-protein-C and anti-protein-S were significantly higher (P < 0.001) in both PE (23.88 ± 10.65 MoM and 43.90 ± 20.45 MoM, respectively) and PE + FGR group (15.95 ± 12.62 MoM and 36.02 ± 27.43 MoM, respectively) than in control group (2.23 ± 3.23 MoM and 1.68 ± 4.075 MoM, respectively), in the presence of unchanged levels of IgG isotype.

Conclusions.?In this study, we first found that the production of anti-protein C and anti-protein S antibodies decreases throughout healthy pregnancies, while they circulate in high levels in women with PE and PE/FGR.     

Is there any role of prolidase enzyme activity in the etiology of preeclampsia?

Objective: To evaluate a relationship between preeclampsia and prolidase enzyme activity.

Methods: A prospective cohort study of 41 pregnant women diagnosed with preeclampsia and 31 healthy pregnant women as control group was selected at Harran University Hospital Department of Obstetrics and Gynecology. The prolidase enzyme activity was analyzed in maternal and umbilical cord plasma, amniotic fluid and placental and umbilical cord tissues by Chinard method in addition to maternal serum levels of lactate dehydrogenase (LDH), serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT).

Results: A significant relationship was found between plasma prolidase activity (635?±?83?U/L) (p =?0.007), umbilical cord plasma prolidase activity (610?±?90?U/L) (p?=?0.013), amniotic fluid prolidase activity (558?±?100?U/L) (p =?0.001), umbilical cord tissue prolidase activity (4248?±?1675?U/gr protein) (p =?0.013) and placental tissue prolidase activity (2116?±?601?U/gr protein) (p =?0.001) in preeclamptic group when compared to healthy pregnant women.

Conclusion: There is a strong correlation between prolidase enzyme activity and preeclampsia. Prolidase enzyme activity may play a role in preeclampsia.     

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.     

Total plasma fibronectin as a marker of pregnancy-induced hypertensive disorders: A longitudinal study

Objective: To determine normal values of total plasma fibronectin in all three gestational trimesters and to examine 1) whether total plasma fibronectin levels differ between normotensive, hypertensive, and preeclamptic women; and 2) whether total plasma fibronectin may serve as an early marker of pregnancy-induced hypertensive disorders.Methods: Total plasma fibronectin was measured in 376 nulliparous women once in each trimester of pregnancy. Normotensive controls (n = 222) and subjects with pregnancy-induced hypertensive disorders (n = 154) were identified after delivery. The group with pregnancy-induced hypertensive disorders was subdivided into a gestational hypertensive group (n = 125) and a preeclamptic group (n = 29). A complete total plasma fibronectin data set was obtained from 347 subjects. Trends in total plasma fibronectin values were compared for the different groups and relative risks (RRs) were calculated after optimal cutoff levels had been determined by receiver operating characteristic curves.Results: Total plasma fibronectin values (standard error of the mean) were 227 ± 3 mg/L in the first, 219 ± 3 mg/L in the second, and 260 ± 5 mg/L in the third trimesters in normotensive pregnancies. In the first trimester and persisting throughout pregnancy, total plasma fibronectin levels were significantly higher in patients with pregnancy-induced hypertensive disorders than in controls and showed a sharper increase throughout pregnancy. Increased first-trimester total plasma fibronectin levels result in an RR of 1.4 (95% confidence interval [CI] 1.1, 1.8) of developing a pregnancy-induced hypertensive disorder in general. The RR for the development of preeclampsia was 1.7 (95% CI 0.9, 3.4), which was not significant, when the first-trimester total plasma fibronectin level was above the cutoff level of 240 mg/L. The RR for developing preeclampsia was 3.8 (95% CI 1.8, 8.0) when the second-trimester total plasma fibronectin level increased above 230 mg/L.Conclusion: The findings of the present study confirm those of previous studies that have found increased total plasma fibronectin levels in pregnancy-induced hypertensive disorders. This study discovered that in these women, total plasma fibronectin levels are elevated in the first trimester. Total plasma fibronectin appears to be a poor predictor of preeclampsia when measured in a general pregnant population. Therefore, total plasma fibronectin should not be used as a routine screening test in a low-risk population. However, obstetricians may use total plasma fibronectin values to help determine the relative risk of developing pregnancy-induced hypertensive disorders.     

Lower vitamin D levels during the second trimester are associated with developing gestational diabetes mellitus: an observational cross-sectional study

Abstract

In this study, we aimed to compare serum 25(OH)D levels in women with and without gestational diabetes mellitus (GDM), and to identify the serum 25(OH)D levels associated with GDM. We recruited 40 women with GDM and 40 healthy pregnant women, aged 20–40?years and in the second trimester, at Gulhane Education and Research Hospital. We excluded women with chronic diseases, preeclampsia, pre-GDM, multiple pregnancies, and those taking medications related to calcium or vitamin D metabolism. We took anthropometric measurements and blood samples during the second trimester. Of the 80 pregnant women, pre-pregnancy body mass index was significantly higher among the GDM group than the healthy group (26.4?±?5.73?kg/m² vs. 22.6?±?3.56?kg/m², p?=?.001). Serum 25(OH)D levels in women with GDM were significantly lower than those in healthy women (16.8?±?9.90?ng/mL vs. 20.9?±?8.16?ng/mL, p?=?.016). The prevalence of severe vitamin D deficiency was as high as 72.5% among women in the GDM group, with a 1.74-fold increased risk of deficient status. Levels of 25(OH)D lower than a cutoff value of 14.0?ng/mL were determined to be related to GDM. These study results suggest that maternal vitamin D deficiency in mid-pregnancy is significantly associated with development of GDM.