Comparison of interleukin-6 levels in maternal and umbilical cord blood in early- and late-onset preeclampsia

Purpose: Increased inflammatory response and cytokines are claimed to play a significant role in the etiology of preeclampsia. Interleukin-6 (IL-6) is a proinflammatory cytokine. Limited number of studies evaluating IL-6 levels in preeclamptic patients have produced conflicting results. Therefore, the present study sought to compare maternal and umbilical cord serum levels of IL-6 in early- and late-onset preeclamptic pregnancies as well as in normal pregnancies. Materials and methods: A total of 69 participants were enrolled in the study. The control group consisted of 24 participants with normal pregnancies. Preeclampsia group consisted of 45 participants. The preeclampsia group was further classified into the subgroups of early- and late-onset preeclampsia. Late-onset preeclampsia group consisted of 24 women whereas early-onset preeclampsia group consisted of 21 women. Serum and umbilical cord samples of IL-6 were compared. Results: There was no significant difference between maternal and umbilical cord serum IL-6 concentrations between the preeclampsia and control group. No significant difference was observed in maternal and umbilical cord serum IL-6 levels between early- and late-onset preeclampsia groups. Conclusion: Our results do not support an increase in IL-6 levels in patients with early- and late-onset preeclampsia. The clinical relevance of our findings needs to be further investigated.     

VEGF,PIGF and HIF-1α in placentas of early- and late-onset pre-eclamptic patients

Abstract

Purpose: The aim of this study was to compare the VEGF, PIGF, and HIF-1α levels in the placentas of early- and late-onset pre-eclamptic patients, which are thought to be important in pathophysiology of pre-eclampsia.

Material and method: Pre-eclamptic early-onset (n?=?22) and late-onset (n?=?24) pregnant women and a control group of healthy pregnant women (n?=?22) were recruited for this case–control study. A semi-quantitative immunohistochemical analysis of VEGF, PIGF and HIF-1α was performed in cross-sections of the placentas of the subjects, after which results were compared.

Results: Levels of VEGF and PIGF in the placentas of pre-eclamptic patients were found to be lower than the levels in the placentas of healthy pregnant women (p?<?0.001 and p?=?0.025, respectively), whereas the levels of HIF-1α were found significantly higher (p?<?0.001). No difference was observed in terms of VEGF, PIGF and HIF-1α in a comparison of the early- and late-onset pre-eclampsia groups (p?>?0.05).

Conclusion: The results of the study indicated that there is no relationship between the time of onset of pre-eclampsia and the placental changes that occur in these factors.     

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.     

Polymorphisms of the angiotensin converting enzyme gene in early-onset and late-onset pre-eclampsia

Objective.?The aim of this study was to investigate differences in maternal and infant ACE genotypes in early-onset and later-onset pre-eclampsia/toxemia (PET).

Methods.?We conducted a case–control study of 22 cases of early-onset pre-eclampsia (before 34 weeks gestation), 38 cases of later-onset pre-eclampsia (after 34 weeks gestation), and 108 healthy controls delivered at term (38–40 weeks gestation) within a stable Caucasian population. Maternal venous blood and cord bloods were obtained for serum angiotensin converting enzyme (ACE) activity, ACE genotype, and acid–base status.

Results.?Mothers who developed early-onset PET were more likely to be homozygous for the deletion allele of the ACE genotype (DD) than mothers with late-onset PET or uncomplicated pregnancies (12/22 (55%) vs. 7/38 (18%) vs. 22/105 (21%), respectively; OR 2.96 [95% confidence intervals (CI) 1.37–6.31]. Infants of mothers with early-onset PET were more likely to be homozygous for the DD genotype than infants of mothers with late-onset PET or controls (7/19 (37%) vs. 9/36 (25%) vs. 11/78 (14%); OR 2.51 (95% CI 1.12–5.61). There were no differences in maternal or infant ACE activities in relation to onset of pre-eclampsia.

Conclusions.?Our findings suggest an association between the DD genotype of the ACE gene and early-onset but not later-onset pre-eclampsia which may give a partial explanation for the higher recurrence risk with early-onset pre-eclampsia.     

Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion

Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p?<?0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p?<?0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.     

Chitotriosidase and YKL-40 in normal and pre-eclamptic pregnancies

OBJECTIVE: To compare macrophage activation in normal and pre-eclamptic pregnancies by determining YKL-40 concentration and chitotriosidase activity in maternal and cord serum. METHODS: In this prospective case-control study samples of maternal peripheral blood and umbilical venous blood were collected from 28 pre-eclamptic and 24 normotensive pregnant women and their newborns. YKL-40 concentration and chitotriosidase activity were determined by enzyme-linked immunoassay and fluorometry, respectively. RESULTS: Chitotriosidase activity in maternal and cord serum and YKL-40 concentration in cord serum were significantly higher in pre-eclamptic pregnancies (P<0.001), but there was no significant difference in maternal serum levels of YKL-40 between the case and control groups (P>0.05). There was a significant positive correlation between diastolic blood pressure and (1) chitotriosidase activity in both maternal and cord serum and (2) cord serum concentration of YKL-40 (r=0.61, r=0.84, and r=0.58, respectively). CONCLUSION: This study may be the first to demonstrate maternal and fetal macrophage activation in pre-eclampsia.     

Carcinoembryonic antigen (CEA) in normal and pre-eclamptic pregnancies (values in maternal blood,amniotic fluid and umbilical cord blood)

Values of Carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 100 pregnant women divided into 4 groups. In group 1 (49 normal pregnancies) and 2 (17 pre-eclamptic pregnancies), the estimation of CEA was done in maternal vein blood, umbilical cord blood and in amniotic fluid. In group 3 (20 normal pregnancies) CEA was measured separately in blood of the two umbilical vessels as well as in maternal vein blood. In group 4 (14 pregnancies with small-for-date infants) CEA was estimated in umbilical cord blood. The values in amniotic fluid of normal and pre-eclamptic pregnancies were more than 20 times higher than in the other two compartments. A significant correlation was found between the amniotic fluid and umbilical cord blood values (r = 0.500; P < 0.05), as well as between the values in umbilical artery and vein (r = 0.792; P < 0.001). Thus, it is thought that CEA is transferred from the amniotic cavity to the umbilical cord while a part of CEA perhaps is produced by the placenta. Umbilical cord blood values of small-for-date fetuses do not differ significantly from the normal. On the contrary, significantly lower values were obtained in umbilical cord blood and in amniotic fluid of pre-eclamptic women as compared to the normal, but this finding is not useful clinically because of the large standard deviation.     

Association between maternal serum 25-hydroxyvitamin D level and pre-eclampsia

Objectives: The objective of the study was to evaluate the association of maternal plasma levels of 25-hydroxyvitamin D (25(OH)D) at late second and third trimester and the risk of pre-eclampsia.

Methods: In this prospective cohort study, maternal plasma 25(OH)D levels were measured at late second and third trimester in 77 women who later developed pre-eclampsia (31 non-severe and 46 severe cases) and 180 women without pre-eclampsia.

Results: The mean gestational age of the timing of the blood sampling was 31.1?±?4.4 at control group, 32.6?±?5.7 at non-severe pre-eclamptic group and 32.3?±?5.4 at severe pre-eclamptic group. The mean 25(OH)D concentration was significantly low in severe pre-eclampsia group (5.8?±?4.5?ng/ml) than non-severe pre-eclampsia (11.8?±?7.3?ng/ml, p?=?0.039) and control groups (14.9?±?12.0?ng/ml, p?<?0.0001). There was no statistically significant difference in 25(OH)D concentration between non-severe pre-eclamptic and control groups (p?=?0.404). In women with 25(OH)D concentration <20?ng/ml, a 12.45-fold increase in the odds of severe pre-eclampsia were detected.

Conclusion: Women with severe pre-eclampsia had low serum 25(OH)D levels. The correlation between maternal 25(OH)D levels and aspartate aminotransferase, alanine transaminase, serum creatinine levels, platelet count were not determined. 25(OH)D levels may be used as an independent predictive marker of severe pre-eclampsia.     

Comparison of maternal and umbilical cord blood soluble lectin-like oxidized low-density lipoprotein receptor 1 levels in early- and late-onset preeclampsia

Background

The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE).

Materials and methods

A case–control study was conducted in pregnant women with early-onset (before 34 weeks’ gestation n = 19) and late-onset (after 34 weeks’ gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels.

Results

The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age.

Conclusions

According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.     

Adiponectin and insulin resistance in early- and late-onset pre-eclampsia

OBJECTIVE: To evaluate the importance of adiponectin and insulin resistance in early- and late-onset pre-eclampsia. DESIGN: A nested case-control study in 72 pregnant women who participated in the first-trimester Down-syndrome-screening programme and who delivered at our hospital. SETTING: University Hospital, Department of Obstetrics and Gynecology. POPULATION: Pregnant women: 36 women with pre-eclampsia of which 20 late onset and 16 early onset were compared with 36 uncomplicated pregnancies who delivered at term. METHODS: In all the women, insulin resistance was calculated by the homeostasis model assessment ratio (HOMA-IR) and plasma adiponectin was determined using an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Insulin resistance and adiponectin concentration. RESULTS: First-trimester plasma adiponectin mean levels in the whole pre-eclampsia group were significantly lower than that in the control group (8.4 +/- 3.3 versus 14.8 +/- 4.6 microgram/ml; P < 0.001), whereas first-trimester mean HOMA-IR values were significantly higher in the pre-eclampsia group than that in the control group (2.0 +/- 1.1 versus 1.0 +/- 0.4; P= 0.01). Plasma adiponectin concentrations at delivery in the pre-eclampsia group were significantly higher than that in the control group (9.2 +/- 3.7 versus 7.8 +/- 2.6 microgram/ml; P= 0.04). First-trimester plasma adiponectin mean concentrations in the late-onset subgroup were significantly lower compared with the concentrations in early-onset subgroup (6.2 +/- 1.4 microgram/ml versus 11.1 +/- 3.2 microgram/ml; P < 0.001), and there was a significant difference in adiponectin plasma values only between women in the late-onset pre-eclampsia group versus those in the control group (P < 0.001). First-trimester mean HOMA-IR values were significantly higher in the late-onset subgroup compared with that of the early-onset subgroup (2.5 +/- 1.3 versus 1.3 +/- 0.3; P= 0.02), and there was a significant difference only between the control group versus the late-onset subgroup (P= 0.001). CONCLUSIONS: First-trimester adiponectin and HOMA-IR values seem to select two completely different populations: early- and late-onset pre-eclampsia, which might suggest a different pathogenesis.     

Angiogenic growth factors in maternal and fetal serum in concordant and discordant twin pregnancies

Abstract

Objective: To assess soluble fms-like tyrosin kinase 1 (sFlt-1), free vascular endothelial growth factor (f-VEGF) and the f-VEGF/sFlt-1 quotient in twin pregnancies, and to determine if they are impaired in discordant twins.

Methods: Case-control study between 18 discordant and 46 concordant twin pregnancies. Angiogenic growth factors were measured in maternal serum during pregnancy and in umbilical artery and vein at birth.

Results: Discordant twins were more often conceived by assisted reproductive techniques than concordant twins. Maternal plasma f-VEGF was significantly lower in discordant twins (p?=?0.04). F-VEGF and f-VEGF/sFlt-1 in the whole sample show a significant higher level in concordant twins. When we analyzed umbilical cord angiogenic factors, the smaller twin had a lower f-VEGF/sFlt-1 quotient (p?=?0.01). We found no correlations between maternal or umbilical growth factors and placental or fetal weight. No difference was found in veno-arterial levels of angiogenic factors in each twin; however, there was a significant rise in arterial f-VEGF (p?=?0.06) in discordant twins.

Conclusion: Mothers of discordant twins have a more anti-angiogenic environment compared to those of concordant twins. We also found an anti-angiogenic environment in the small twin when we compared umbilical vein angiogenic factors against its big co-twin.     

Metastin levels in pregnancies complicated by pre-eclampsia and their relation with disease severity

Aims: To evaluate the role of metastin levels in the pathophysiology of pre-eclampsia and to determine whether there is a relationship between the severity of the disease and Doppler velocimetry measurements. Methods: This cross-sectional study included 89 pregnant women (50 healthy normotensive pregnant women, 15 patients with mild pre-eclampsia, and 24 patients with severe pre-eclampsia) at the third trimester of pregnancy. The maternal levels of plasma metastin were determined by enzyme-linked immunosorbent assay. The umbilical artery and uterine artery blood flow velocities were measured by transabdominal color and pulsed Doppler ultrasound. Results: Plasma metastin levels were lower in patients with pre-eclampsia than those in the normotensive pregnant women. Four patients with mild pre-eclampsia and seven patients with severe pre-eclampsia had abnormal Doppler velocimetry findings. Metastin levels of pre-eclamptic patients with abnormal Doppler velocimetry findings were significantly lower than those in patients with normal Doppler velocimetry findings. Plasma metastin levels negatively correlated with proteinuria in 24 hours and with mean arterial pressure in the cases of pre-eclampsia. Conclusions: The findings suggest that decreased maternal concentrations of plasma metastin may be involved in the pathogenesis of pre-eclampsia. Plasma metastin levels may be useful in the assessment of the severity of pre-eclampsia. However, further trials are needed to clarify the role of metastin in pre-eclampsia.     

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.     

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Abstract

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.

Methods: This cross-sectional study included women with preeclampsia (n?=?106) and women with an uncomplicated pregnancy (n?=?131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.

Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p?<?0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p?=?0.7 and p?=?1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman’s Rho?=?0.72 and 0.63; each p?<?0.0001), and negatively with PlGF (Spearman’s Rho?=??0.56, p?<?0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (<37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.

Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.     

Ultrastructure of human umbilical vessels in pre-eclampsia

Objective: Our objective in this study was to investigate the ultrastructure of endothelial and muscle cells of human umbilical vessels in both normal and pre-eclamptic pregnancies. Methods: Ten umbilical cords from pre-eclamptic (36, 38 and 40 weeks) and four from normal pregnancies (40 weeks) were collected immediately after vaginal deliveries. Umbilical veins and arteries were isolated and fixed in phosphate-buffered 2.5% glutaraldehyde solution (pH 7.2) for 4 h and postfixed with 1% osmium tetroxide at 4°C for 2 h. The sections were embedded in Araldit CY 212. Ultrathin sections were stained with uranyl acetate, examined and photographed. Results: Human umbilical vessel endothelial cells showed ultrastructural changes in pre-eclamptic patients. Weibel–Palade bodies and some organelles such as rough endoplasmic reticulum were found in increased numbers in venous endothelial cells. Accumulations of granular material were detected under the venous endothelium. Conclusion: The endothelial and muscle cells of the umbilical vessels from pregnancies complicated by pre-eclampsia showed morphological changes.     

Fetal endothelium dysfunction is associated with circulating maternal levels of sE-selectin,sVCAM1, and sFlt-1 during pre-eclampsia

Objectives.?To evaluate the association between endothelial activation markers in the maternal circulation with nitric oxide (NO) synthesis in human umbilical endothelial cells.

Study design.?This is a case-control study of normal and pre-eclamptic pregnancies. The levels of sE-selectin, soluble vascular cell adhesion molecule 1 (sVCAM-1), and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured by enzyme-linked immunosorbent assay, and histamine-induced NO synthesis was detected by fluorometric examination of the human umbilical vein endothelial cells (HUVECs) isolated from normal and pathological pregnancies.

Results.?Mothers with severe pre-eclamptic pregnancies have premature and smaller babies than mothers with normal pregnancies (P?<?0.05); they also have high maternal plasma levels of sVCAM-1 (～2-fold), sFlt-1 (～2.5-fold), and lower (～70%) histamine-stimulated NO synthesis in HUVECs. A positive relationship between systolic blood pressure (SBP) and plasma levels of sE-selectin, sVCAM-1, and sFlt-1 was demonstrated. Moreover, levels of sE-selectin, sVCAM-1, and sFlt-1 were negatively associated with newborn weight (NBW), gestational age at delivery, and NO synthesis. Women with high E-selectin (>63?ng/ml), VCAM-1 (>752?ng/ml), and sFlt-1 (>15204 pg/ml) showed high risk (～2-fold) for preterm delivery and very preterm delivery, or fetal weight <1500?g (～1.5-fold) compared with women with low levels.

Conclusions.?High circulating levels of maternal endothelial dysfunction markers present in pre-eclampsia are associated with decreased NO synthesis in fetal endothelium.     

Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction

OBJECTIVE: To evaluate placental morphology in pregnancies complicated by early- and late-onset pre-eclampsia (PET) with and without fetal growth restriction (FGR) using stereological techniques. DESIGN: A total of 69 pregnant women were studied. Twenty women had pregnancies complicated by PET, 17 by FGR and 16 by both PET and FUR; the remaining 16 were from gestational-age-matched controls. Each group was further classified into early onset (<34 weeks) and late onsets (>34 weeks) based on gestational ages. SETTING: NPIMR at Northwick Park and St Marks Hospital. POPULATION: placentae from pregnant women. METHODS: Formalin-fixed, wax-embedded sections stained with anti-CD34 antibodies and counterstained with haematoxylin. MAIN OUTCOME MEASURES: Volumes, surface areas, lengths, diameters and shape factors of the villous tissues and fetal vasculature in the intermediate and terminal villi of all the groups studied. RESULTS: Terminal villi volume and surface area were compromised in early-onset PET cases, late-onset PET had no impact on peripheral villi or vasculature features. The morphology of the vascular and villous subcomponents in the intermediate and terminal villi was significantly influenced by late-onset FGR, whereas early-onset FGR caused a reduction in placental weight. Length estimates were not influenced by PET, FGR or age of onset. Intermediate arteriole shape factor was significantly reduced in late-onset FGR. CONCLUSIONS: Isolated early-onset PET was associated with abnormal placental morphology, but placentas from late-onset PET were morphologically similar to placentas from gestational-age-matched controls, confirming the existence of two subsets of this condition and supporting the hypothesis that late-onset PET is a maternal disorder and not a placental disease.     

Comparison of maternal and cord blood nucleated red blood cell count between pre-eclamptic and healthy women

AIM: The aim of this study was to evaluate the influence of pre-eclampsia on the cord and maternal nucleated red blood cell (NRBC) count. METHODS: Immediately after delivery, 1 mL of maternal venous blood and 1 mL of cord blood from 50 pre-eclamptic and 150 healthy pregnant women were collected separately in tubes containing 1.5 mg ethylene diamine tetra-acetic acid. Blood smears were prepared and stained using the Giemsa method. The number of NRBC per 100 leukocytes in maternal and cord blood was counted and compared between the two groups using SPSS software package for Windows. Any correlation of the NRBC count in maternal and umbilical cord blood was also evaluated. P-values < 0.05 were considered significant. RESULTS: The mean (+/-SD) NRBC per 100 white blood cell (WBC) level in cord blood of newborns in the pre-eclamptic group (18.2 +/- 31.8, range 0-142) was significantly greater than in the control group (6.2 +/- 8.1, range 0-36). Low birth weight and intrauterine growth restriction showed a statistically significant relationship with abnormal NRBC count in pre-eclamptic patients. A significant correlation was found between the maternal and cord blood NRBC count in the pre-eclamptic group. CONCLUSION: Fetal response to utero-placental insufficiency in pre-eclampsia leads to elevated NRBC in the cord blood, particularly in the presence of low birth weight and intrauterine growth restriction. The positive correlation between maternal and cord blood NRBC counts in pre-eclamptic patients indicates that maybe the hypoperfused placenta plays a role in the correlated alteration of the maternal and fetal NRBC count.     

Interleukin-6 levels in umbilical artery serum in normal and abnormal pregnancies.

OBJECTIVE: The aim of our study was to determine the correlation of abnormal umbilical artery interleukin-6 levels with pregnancies complicated by preterm delivery and pre-eclampsia. METHOD: Cord serum (umbilical artery) was collected at delivery by cesarean section or spontaneous delivery. Samples were retrieved from patients with normal and abnormal pregnancies. Patients were divided into three groups: group 1, a control group of samples from uncomplicated pregnancies (n = 24); group 2, patients with pre-eclampsia (n = 21); and group 3, patients having had preterm delivery (n = 29). Interleukin-6 was measured by bioassays. Statistics were performed with the Mann-Whitney U-, Student's t- and the Kruskal-Wallis tests. RESULTS: Interleukin-6 levels in women with preterm delivery were statistically higher compared to those of normal pregnancies (P < 0.05) and lower in the cord serum of pre-eclamptic when compared to those of normal pregnancies (P < 0.05). CONCLUSION: In conclusion, we believe that further investigations could elucidate the role of this pleiotropic cytokine in both, normal and pathologic reproductive biology, and determine the clinical utility of IL-6 measurements in obstetric practice.     

Differential levels of interleukin 6 in maternal and cord sera and placenta in women with pre-eclampsia

BACKGROUND: Interleukin 6 (IL-6) is a T helper 2 cytokine with a variety of properties including pro-inflammatory characteristics. It has, therefore, been implicated in the pathophysiology of abnormal pregnancies. Objective: To investigate the association between IL-6 and pre-eclampsia by estimating the differential levels of IL-6 in maternal and cord serum and supernatant of homogenized placental tissue. METHODS: 50 primigravidae with pre-eclampsia and 50 matched normotensive primigravidae served as controls. At delivery, maternal and cord blood were collected and the serum extracted. Placental blocks were homogenized and sonicated in RPMI solution and the supernatant collected. The total protein concentration was determined and IL-6 levels assayed with an ELISA technique. RESULTS: Placental IL-6 (170 and 186 pg/mg protein) was threefold that in the maternal (64 and 58 pg/mg protein) and cord serum (63 and 72 pg/mg protein; p < 0.01). There was no significant difference in the mean IL-6 levels in maternal and cord serum or placenta in both pre-eclamptic women and normotensive controls nor in pre-eclamptic patients with babies with intra-uterine growth restriction or in pre-eclamptic patients with babies with an appropriate birth weight and in normotensive controls. CONCLUSION: There are no differences in the maternal and cord sera and placental levels of IL-6 in pre-eclamptic and normotensive women, indicating that IL-6 may not have a role in the pathophysiology of pre-eclampsia.