Evaluation of maternal serum progranulin levels in normotensive pregnancies,and pregnancies with early- and late-onset preeclampsia

Aims: To investigate the possible pathophysiological associations between progranulin (PGRN) and preeclampsia (PE), early-onset PE (EOPE) and late-onset PE (LOPE).

Study design: A cross-sectional study was designed to include consecutive patients with uncomplicated pregnancy (n?=?28), EOPE (n?=?30) and LOPE (n?=?22). Maternal levels of serum PGRN were measured with the use of an enzyme-linked immunosorbent assay kit.

Results: The mean serum PGRN level was significantly higher in women with PE compared to the control group (54.17?±?4.20?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001), in the LOPE group compared to the control group (51.63?±?4.61?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001) and also in women with EOPE compared to women with LOPE (56.03?±?2.68?pg/ml versus 51.63?±?4.61?pg/ml, p?<?0.001). Serum PGRN was negatively correlated with gestational age at birth (r?= ?0.669, p?=?0.001) and birth weight (r?= ?0.653, p?=?0.001); and positively correlated with systolic (r?=?0.653, p?=?0.001) and diastolic blood pressure (r?=?0.601, p?=?0.001), C-reactive protein (r?=?0.519, p?=?0.001), uterine artery pulsatility (r?=?0.441, p?=?0.001) and resistance indices (r?=?0.441, p?=?0.001).

Conclusions: Serum PGRN levels increase significantly in women with PE as an indirect sign of placental dysfunction. This increase is even more prominent in women with EOPE. The serum PGRN in the third trimester is positively correlated with gestational age at birth and birth weight.     

Comparison of angiogenic and anti-angiogenic factors in maternal and umbilical cord blood in early- and late-onset pre-eclampsia

Purpose: The aim of this study was to compare maternal and umbilical cord serum levels of the angiogenic and anti-angiogenic factors in early- and late-onset pre-eclamptic pregnancies as well as in normal pregnancies, which might have significant importance in the etiology of pre-eclampsia. Materials and Methods: This prospective case-control study was carried out with pre-eclamptic (early-onset, ≤?34 weeks and late-onset, >34 weeks) and normal pregnant women. VEGF, PIGF, sFlt-1 and sEng levels in maternal and umbilical cord serum were measured before delivery and the findings were compared. Results: The study was conducted with 15 early- and 15 late-onset pre-eclampsia patients, and 17 patients with normal pregnancies. It was found that sEng levels were higher in the umbilical cord serum in the early-onset and in the maternal serum in the late-onset pre-eclampsia group than the control group (p < 0.05). No significant difference in any factor was observed between the early- and late-onset pre-eclampsia groups. Conclusion: In this study, the results showed that angiogenic and anti-angiogenic factor levels in maternal serum and umbilical cord serum may not be related to the time of onset of pre-eclampsia.     

Comparison of clinical and laboratory findings in early- and late-onset preeclampsia

Abstract

Objective: To compare clinical and laboratory findings between the early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP).

Methods: This prospective longitudinal study was performed at a tertiary referral university clinic. All patients meeting the inclusion criteria were divided into two groups, the EOP group and the LOP group, according to gestational age at the onset of disease. The distinction criterion for early versus late onset was set as week 34 of gestation. Clinical and laboratory findings, and maternal–perinatal outcomes were compared between the groups.

Results: A total of 157 patients with preeclampsia were included. A significant difference was observed between the groups in terms of diagnosis and severity of the disease (p?=?0.007 and <0.001, respectively). The history of previous preeclampsia, diastolic blood pressure and hourly urine output on admission to the hospital were significantly different between the groups (p?=?0.016, 0.018 and 0.024, respectively). Latent period for delivery and postpartum hospitalization time were longer in the EOP group than in the LOP group (p?=?0.024 and 0.002, respectively). The patients with EOP received betamethazone (p?<?0.001) and MgSO₄ (p?=?0.029) more frequently. Neonatal characteristics such as birth weight, low APGAR score and admission to neonatal intensive care unit were significantly different between the groups (p?<?0.001, for all variables). Total proteinuria at 24?h was found significantly higher in the EOP group than in the LOP group (p?=?0.012).

Conclusion: The results confirmed the opinion that EOP is a distinct and more severe clinical entity than LOP. In particular, higher proteinuria is associated with EOP.     

Comparison of indications of pregnancy termination and prognosis of mothers and neonates in early- and late-onset preeclampsia

Objective: To compare the indications of pregnancy termination and prognosis between early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP). Methods: In total, 100 patients diagnosed early-onset preeclampsia in our hospital from January 1, 2012, to June 30, 2014, were recruited for this retrospective cohort study. At the same time, we randomly chose another 100 late-onset preeclampsia as the contrast group. Criterion distinguishing early versus late was set at week 34 of gestation. Indications for pregnancy termination and prognosis of mothers and neonates were compared between the groups. Results: Significant differences were observed between the groups regarding indications for terminating pregnancy. The EOP indications to terminate the pregnancy were mainly fetal-related, while LOP were mainly maternal-related. Postpartum neonatal morbidity and mortality were significantly higher, mean gestational age onset and delivery were significantly earlier, latent period for delivery and postpartum hospitalization time were significantly longer, admission 24 h proteinuria was significantly higher in EOP than in LOP group (P < 0.05). Conclusion: EOP is a distinct and more severe clinical entity with earlier gestational age onset and delivery. EOP might be a fetal-related disease complicated by severe placental and perinatal injuries; LOP might be a maternal-related derived disease condition.     

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.     

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.     

Serum collectrin levels in patients with early- and late-onset preeclampsia

Aim: The aim of this study is to investigate the maternal levels of collectrin in early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE). To assess the correlation between serum collectrin levels and blood pressure in humans.

Material and methods: This cross-sectional study was conducted including 79 pregnant women, 27 with normal pregnancy, 30 with EOPE and 22 with LOPE. Maternal serum levels of collectrin were measured by using enzyme-linked immunosorbent assay kits.

Results: The mean serum collectrin level was significantly lower in women with PE compared with the control group (8.49?±?3.12?ng/ml (EOPE), 9.69?±?3.01?ng/ml (LOPE) versus 11.51?±?4.33?ng/ml) and was found to be the lowest in the EOPE group (8.49?±?3.12?ng/ml). The mean serum urea and uric acid levels were significantly higher in the PE group than the control group. Serum collectrin concentrations did not correlate with maternal age, BMI and serum creatinine levels. However, collectrin concentrations were negatively correlated with systolic blood pressure (r?=??0.284, p?=?.011) and diastolic blood pressure (r?=??0.275, p?=?.014) as well as with maternal serum urea (r?=??0.269, p?=?.017) and uric acid (r?=??0.219, p?=?.049) concentrations.

Conclusion: Maternal serum collectrin levels are significantly lower in patients with preeclampsia than in the control group. There is an inverse correlation between serum collectrin levels and blood pressure.     

Do the physiological aging of the placenta and the changes in angiogenesis marker sFlt-1 and PlGF concentrations predispose patients to late-onset preeclampsia?

Objective: Aging of the placenta is associated with natural processes that impair its functions. The processes are related to both oxidative stress exacerbation and the occurrence of higher concentrations of disordered angiogenesis markers. Both these types of processes are known to play roles in the development of preeclampsia. We attempted to show that natural ageing of the placenta can be one of the cofactors contributing to the development of late-onset preeclampsia.

Patients, materials and methods: 159 pregnant patients were divided into four groups: Two of preeclampsia patients and two of patients with physiological pregnancies, depending on the gestational age. For each group, disordered angiogenesis markers sFlt-1 and PlGF before and after 34 weeks of gestation and in particular stages of gestation were analyzed.

Results: Lower PlGF and sFlt-1/PlGF ratio values were found in cases of late-onset preeclampsia. In physiological pregnancies, sFlt-1 values were observed to increase and PlGF values to decrease with gestational age. An association was shown to exist between disordered angiogenesis markers and gestational age both in preeclampsia and physiological pregnancies.

Conclusions: (1) Analyses of disordered angiogenesis markers in early- and late-onset preeclampsia patients and patients with physiological pregnancies allow for a suggestion that natural “ageing of the placenta” and placental hypoperfusion lesions exacerbating with the advancing gestational age are some of the causes of late-onset preeclampsia. (2) Cases of early-onset preeclampsia are associated with more severe changes of disordered angiogenesis marker concentrations, which may be indicative of a more considerable impairment of placental perfusion in such patients. (3) In the course of the physiological pregnancy, there is a gradual increase in sFlt-1 and decrease in PlGF, which implies an elevated angiogenesis disorder that progresses with the gestational age.     

Effect of preeclampsia and intrauterine growth restriction on endothelial progenitor cells in human umbilical cord blood

Objectives: Endothelial progenitor cells (EPCs) might play important roles in vascular homeostasis. This study evaluated the influence of prematurity, preeclampsia (PE) and intrauterine growth restriction (IUGR) on the EPC population in human umbilical cord blood (CB). Methods: CB was obtained from 19 preterm and 27 term deliveries. Mononuclear cells were isolated by gradient centrifugation and subjected to flow cytometry to obtain percentages of CD45(d) CD34+, CD45(d) CD133+, CD 45(d) CD34+ CD133+, and CD45(d) CD34+ CD133+ VEGFR-2+ cells. Clinical data were obtained using chart review. Results: Percentages of EPCs were comparable between preterm and term cord blood. CD45(d) CD34+ CD133+ cells were significantly decreased in CB samples obtained from women with PE (n = 14) [0.01, (0.00–2.6), [median, (range)], as compared to those without PE (n = 32) [1.74 (0.00–3.1)] (p = 0.005). CD45(d) CD133+ CD34? cells were significantly increased in presence of PE [0.43, (0.06–1.38)], (p = 0.002). CD45(d) CD34+ CD133+ cells were significantly decreased in presence of IUGR, with no change in CD45(d) CD133+ CD34? cells. Differences in EPC types associated with PE and IUGR were present only in term CB. Conclusions: Exposure to PE and IUGR is associated with significant changes in EPC population. Future studies are needed to explore the clinical impact of observed changes.     

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.     

Th1, Th2, Th17 and Treg levels in umbilical cord blood in preeclampsia

Introduction: Preeclampsia is one of the major causes of maternal and neonatal mortality. During pregnancy, the immune system must maintain the tolerance to the fetus, thus changes in the cytokine balance may result in a disturbed pregnancy. T helper cells play an important role in modulation of the immune system and are involved in this cytokine balance.

Objective: Many studies have been performed to study the T cell composition in different compartments during pregnancy, although this is the first study in which T cells are evaluated in umbilical cord blood.

Study design: Intracellular expression of INF-gamma, IL-17, IL-4 and forkhead foxP3 in CD4+ T cells was evaluated in umbilical blood from healthy pregnant and preeclamptic women using a flow cytometer.

Results: Th2 and Treg cells levels were significantly diminished in preeclamptic compared to the healthy women, but no difference in Th1 and Th17 levels were found between both groups.

Conclusions: Our data suggest that the cytokine balance is broken, encouraging the development of an exacerbated inflammatory response. Our results show that there is a shift, in the Th1/Th2, and the Th17/Treg balance, favoring skewness towards a proinflammatory status in the umbilical cord blood in preeclampsia.     

Increased oxidant generation in the metabolism of hypoxanthine to uric acid and endothelial dysfunction in early-onset and late-onset preeclamptic women

Objective: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. Methods: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. Results: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. Conclusions: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.     

In vitro umbilical cord wrapping and torsion: possible cause of umbilical blood flow occlusion

Abstract

Objective: Intrapartum fetal heart rate decelerations and bradycardia are often attributed to umbilical cord occlusion without knowing the anatomic basis of that occlusion. We hypothesized that umbilical cord twisting while looped around fetal parts could occlude blood flow.

Methods: Using an in vitro preparation, human umbilical cord veins were perfused at one end with water at approximately 40?cm H₂O. The cords were looped around pipes that approximated the diameter of fetal body or limb parts, after which the perfused segment of cord was twisted until water flow stopped. The number of rotations needed to stop perfusion was recorded for each length of twisted cord (4, 6 and 8?cm) and for each pipe diameter.

Results: There were 21 completed studies. All cords demonstrated that a decreasing number of twists were needed to stop venous flow as the segment twisted became shorter (from 8 to 4?cm). For each segment length, the number of twists required to stop flow decreased as the pipe diameter narrowed.

Conclusion: This model demonstrates that a wrapped umbilical cord, particularly with a short segment between the placental insertion and the fetal body part, may be predisposed to cord occlusion in response to fetal rotation.     

Trace elements profiles of maternal blood,umbilical cord blood,and placenta in Beijing,China

Aim: Profiles of heavy metals such as chromium (Cr), manganese (Mn), arsenic (As), lead (Pb), and cadmium (Cd), and micronutrients such as ferrum (Fe), copper (Cu), zinc (Zn), and selenium (Se) in maternal and umbilical cord blood clots were investigated for assessing placenta function in the transport of micronutrients or heavy metal pollutants.

Methods: Correlations between contents of elements in the two tissues were also analyzed.

Results: Significantly lower levels of Cr, Pb, and Cd in umbilical cord blood clots than in maternal blood clots, and negative relationship between lead levels in maternal and umbilical cord blood (r?=??.334, p?=?.016). Concentration of Mn in cord blood was significantly higher than that in maternal blood clots and positively related to the maternal level. The data also show that the placenta may work most strongly as a barrier against Cd and protects fetus from its harmful effect, while plays almost no role in preventing the transportation of As, Mn, and Pb.

Conclusions: In conclusion, pregnant women should avoid exposure to environment polluted with heavy metals, particularly with As, Mn, and Pb.     

Decrease and dysfunction of endothelial progenitor cells in umbilical cord blood with maternal pre-eclampsia

BACKGROUND: The pre-eclampsia is characterized by placental defective angiogenesis and maternal vascular/endothelial dysfunction. Recently, the decrease and senescence of endothelial progenitor cells (EPC) has been observed in maternal circulation with pre-eclampsia. Given the essential involvement of EPC in neovascularization and reendothelialization, we investigate whether or not the depletion of EPC is existent in placental/fetal circulation with maternal pre-eclampsia. METHODS: Samples of venous cord blood were collected during the labor of preeclamptic mothers (n = 14) and normotensive controls (n = 10). Circulating EPC were enumerated as AC133+/KDR+ cells via fluorescence-activated cell sorting (FACS) analysis. Additionally, EPC were expanded in vitro and identified by DiI-acLDL uptake and lectin staining by direct fluorescent staining under a laser scanning confocal microscope. EPC proliferation, migration and vasculogenesis activities were determined by MTT, modified Boyden chamber assay and in vitro vasculogenensis assay. RESULT: The placental/fetal circulating EPC numbers were significantly decreased in the pre-eclampsia group compared with the control (median, 200; range, 100-440 cells/mL vs 390; 270-440 cells/mL, P < 0.001), and after in vitro cultivation the numbers of EPC also decreased in pre-eclampsia group (19.5; 5.0-32.0 vs 39.5; 31.2-52.0 EPC/x200 field; P < 0.001). Both circulating EPC and cultivated EPC were inversely correlated with cord blood level of soluble fms-like tyrosine kinase 1 (sFlt-1). In addition, the EPC from patients with pre-eclampsia were significantly impaired in their proliferation, migration and vasculogenesis capacities. CONCLUSION: The present study documented the decrease and dysfunction of placental/fetal circulating EPC in patients with pre-eclampsia. The alteration is probably associated with the increased sFlt-1 levels in the umbilical cord blood.     

Percentiles for gas values in human umbilical cord blood

The distribution of gas values of umbilical cord blood was studied in an university clinic population during a period of 3 yr. All patients in labor were guided by obstetrical personnel and continuous electronic fetal monitoring (CTG). Microblood analyses were performed on indication of the CTG. The tenth percentile for the total population for umbilical artery blood pH was 7.14 and base excess was -12.7 mmol/l. The tenth percentile for pH in umbilical venous blood was 7.23 and base excess was -10.2 mmol/l. Increase of acidemia was seen in the following order: optimal pregnancy and labor, spontaneous vertex delivery, multiparity, primiparity, instrumental and breech delivery. Percentiles of umbilical cord blood gases could serve as an index for the standard of obstetrical care in addition to perinatal mortality and other measures of perinatal morbidity.     

Comparison of clinical and perinatal outcomes in early- and late-onset preeclampsia

Purpose

To compare the clinical and laboratory findings and maternal–perinatal outcomes between women with early-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE).

Methods

One hundred and fifty-four women with preeclampsia (PE) who delivered in our clinic were included in the study. Perinatal and obstetric outcomes were evaluated.

Results

The incidence of abnormal uterine artery (UtA) velocity waveform was significantly higher in the EO-PE group (71.4 vs 30.1 %) (p < 0.001). The incidences of small-for-gestational age, oligohydramnios, Apgar score <7 at 5 min, stillbirth and early neonatal death rates were significantly higher in women with EO-PE compared to LO-PE (p < 0.01). Maternal complications were only recorded in women with severe PE.

Conclusion

EO-PE, especially with abnormal UtA Doppler findings defines a placentation abnormality with higher perinatal adverse outcomes.