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.     

Ionized calcium levels in umbilical cord blood of women with preeclampsia and normotensive pregnancies

Calcium is essential for normal fetal growth and development. During intrauterine life, the fetus is entirely dependent on the mother and a normally functioning placenta for calcium accretion. Preeclampsia is associated with abnormal calcium metabolism and placental dysfunction. The objective of our study was to investigate ionized calcium levels in the umbilical cord arterial blood of women with preeclampsia and normotensive pregnancies. There were 24 women in the preeclampsia group and 25 in the normotensive group. There was no difference in the cord pH and fetal growth restriction between the two groups. Ionized calcium levels were significantly lower in the preeclampsia group (p?<?0.001). Our results emphasize the need for further studies on the calcium status of infants born to mothers with preeclampsia.     

Placental exosomes and pre-eclampsia: Maternal circulating levels in normal pregnancies and,early and late onset pre-eclamptic pregnancies

Introduction and aimExosomes are a subtype of extracellular vesicle (20–130 nm) released by biological cells under normal and pathological conditions. Although there have been reports of circulating exosomes in normal pregnancy, the relevance of placental-derived exosomes in normal and abnormal pregnancies still needs to be elucidated. The aim of this study was to quantify total and placental-derived exosomes in maternal plasma from normal (N), early onset- and late onset-preeclampsia (PE).MethodPlasma samples were obtained from pregnant women in the third trimester, for the isolation of exosomes by differential ultracentrifugation. Total exosomes were quantified using nanoparticle tracking analysis and immuno-reactive exosomal CD63 quantification. Placental-derived exosomes were quantified using placental alkaline phosphatase (PLAP) as a specific marker. The contribution of placental-derived exosomes to total exosomes in maternal plasma was determined by the ratio of PLAP⁺ exosomes to CD63⁺ exosomes.ResultsThe concentration of total exosomes significantly increased in early onset-PE and late onset-PE compared to N (≤33 weeks) and N (≥34 weeks). The relative concentration of placental-derived exosomes significantly increased in early onset-PE but decreased in late onset-PE compared to N. The ratio of PLAP⁺ exosomes to total number of exosomes significantly decreased in early onset-PE and late onset-PE. A positive correlation between total and placental-derived exosomes were obtained in N (≤33 weeks: Pearson's r = 0.60, ≥34 weeks: Pearson's r = 0.67) and early onset-PE (Pearson's r = 0.51, p < 0.05) with the inverse in late onset-PE (Pearson's r = −0.62, p < 0.01).ConclusionThe differences in the contribution of placental-derived exosomes to total exosomes in maternal circulation suggests a possible pathophysiological role of placental-derived exosomes in pre-eclampsia.     

Maternal serum soluble CD30 is increased in normal pregnancy, but decreased in preeclampsia and small for gestational age pregnancies.

OBJECTIVE: Women with preeclampsia and those who deliver small for gestational age (SGA) neonates are characterized by intravascular inflammation (T helper 1 (Th1)-biased immune response). There is controversy about the T helper 2 (Th2) response in preeclampsia and SGA. CD30, a member of the tumor necrosis factor receptor superfamily, is preferentially expressed in vitro and in vivo by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) has been proposed to be an index of Th2 immune response. The objective of this study was to determine whether the maternal serum concentration of sCD30 changes with normal pregnancy, as well as in mothers with preeclampsia and those who deliver SGA neonates. METHODS: This cross-sectional study included patients in the following groups: (1) non-pregnant women (N = 49); (2) patients with a normal pregnancy (N = 89); (3) patients with preeclampsia (N = 100); and (4) patients who delivered an SGA neonate (N = 78). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests with post-hoc analysis were used for comparisons. A p value <0.05 was considered statistically significant. RESULTS: (1) The median sCD30 serum concentration of pregnant women was significantly higher than that of non-pregnant women (median 29.7 U/mL, range 12.2-313.2 vs. median 23.2 U/mL, range 14.6-195.1, respectively; p = 0.01). (2) Patients with preeclampsia had a significantly lower median serum concentration of sCD30 than normal pregnant women (median 24.7 U/mL, range 7.6-71.2 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (3) Mothers with SGA neonates had a lower median concentration of sCD30 than normal pregnant women (median 23.4 U/mL, range 7.1-105.3 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (4) There was no significant correlation (r = -0.059, p = 0.5) between maternal serum sCD30 concentration and gestational age (19-38 weeks) in normal pregnant women. Conclusions: (1) Patients with preeclampsia and those who deliver an SGA neonate had a significantly lower serum concentration of sCD30 than normal pregnant women. (2) This finding is consistent with the view that preeclampsia and SGA are associated with a polarized Th1 immune response and, perhaps, a reduced Th2 response.     

Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction.

OBJECTIVE: In normal pregnancy there is both a neutrophilia and a mild neutrophil activation. In preeclampsia both direct and indirect evidence supports further marked neutrophil activation. In the pathogenesis of preeclampsia peripheral blood neutrophils may play a vital role in communicating between the preeclamptic placenta and the maternal vascular endothelium and contribute to the endothelial cell dysfunction that characterizes the maternal syndrome of preeclampsia. Preeclampsia shares many elements with the systemic inflammatory response syndrome. Neutrophils, key effectors of the systemic inflammatory response syndrome, are associated with hepatic necrosis and adult respiratory distress syndrome, both of which most commonly kill women with preeclampsia. We hypothesized that delayed neutrophil apoptosis could explain (1) the neutrophilia of normal pregnancy and (2) the differential maternal responses to the shared placental abnormality of preeclampsia and normotensive intrauterine growth restriction. STUDY DESIGN: Neutrophils were isolated (dextran 500, Ficoll [Amersham Pharmacia Biotech AB, Uppsala, Sweden], and erythrocyte lysis) from (1) case patients with preeclampsia at 相似文献   

Maternal and fetal circulating angiogenin levels in pregnancies with small-for-gestational-Age and appropriate-for-gestational-Age infants

OBJECTIVE: The objective of the present study was to evaluate whether maternal and fetal circulating angiogenin levels in pregnancies with small-for-gestational- age (SGA) infants are different from those in pregnancies with appropriate-for-gestational-age (AGA) infants. METHODS: Maternal and fetal circulating angiogenin concentrations were compared at birth between 16 pregnancies with SGA (7 delivered vaginally and 9 delivered by elective cesarean section) and 46 pregnancies with AGA (27 delivered vaginally and 19 delivered by cesarean section). Serum angiogenin level was measured with an enzyme-linked immunosorbent assay. RESULTS: There were no significant differences in maternal and fetal serum angiogenin levels between the two groups. However, maternal serum angiogenin levels were significantly higher than those in fetal serum within both SGA and AGA infant pregnancies. There were no significant differences in maternal and fetal serum angiogenin levels between vaginal and cesarean delivered pregnancies in both SGA and AGA groups. CONCLUSION: These results suggest that there is no difference in angiogenin synthesis between SGA and AGA pregnancies.     

Maternal serum soluble CD30 is increased in normal pregnancy,but decreased in preeclampsia and small for gestational age pregnancies

Objective. Women with preeclampsia and those who deliver small for gestational age (SGA) neonates are characterized by intravascular inflammation (T helper 1 (Th1)-biased immune response). There is controversy about the T helper 2 (Th2) response in preeclampsia and SGA. CD30, a member of the tumor necrosis factor receptor superfamily, is preferentially expressed in vitro and in vivo by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) has been proposed to be an index of Th2 immune response. The objective of this study was to determine whether the maternal serum concentration of sCD30 changes with normal pregnancy, as well as in mothers with preeclampsia and those who deliver SGA neonates.

Methods. This cross-sectional study included patients in the following groups: (1) non-pregnant women (N = 49); (2) patients with a normal pregnancy (N = 89); (3) patients with preeclampsia (N = 100); and (4) patients who delivered an SGA neonate (N = 78). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests with post-hoc analysis were used for comparisons. A p value <0.05 was considered statistically significant.

Results. (1) The median sCD30 serum concentration of pregnant women was significantly higher than that of non-pregnant women (median 29.7 U/mL, range 12.2–313.2 vs. median 23.2 U/mL, range 14.6–195.1, respectively; p = 0.01). (2) Patients with preeclampsia had a significantly lower median serum concentration of sCD30 than normal pregnant women (median 24.7 U/mL, range 7.6–71.2 vs. median 29.7 U/mL, range 12.2–313.2, respectively; p < 0.05). (3) Mothers with SGA neonates had a lower median concentration of sCD30 than normal pregnant women (median 23.4 U/mL, range 7.1–105.3 vs. median 29.7 U/mL, range 12.2–313.2, respectively; p < 0.05). (4) There was no significant correlation (r = ?0.059, p = 0.5) between maternal serum sCD30 concentration and gestational age (19–38 weeks) in normal pregnant women.

Conclusions. (1) Patients with preeclampsia and those who deliver an SGA neonate had a significantly lower serum concentration of sCD30 than normal pregnant women. (2) This finding is consistent with the view that preeclampsia and SGA are associated with a polarized Th1 immune response and, perhaps, a reduced Th2 response.     

Maternal serum total cortisol levels in normal and pathologic pregnancies

The effect of pregnancy on maternal serum total cortisol (MSFT) was studied systematically in the course of 90 normal pregnancies (n = 204). Moreover, the evaluation of MSFT determinations in abnormal pregnancies, intrauterine growth retardation (IUGR) and obstetrical complications, premature rupture of the membranes (PROM), premature delivery (PD), and full term pregnancies with post maturity syndrome (PMS) were also investigated. MSFT was measured by an enzyme immunoassay. Gradual increase in MSFT was found from the 6th week of pregnancy to the 40th week of pregnancy and a sharp rise was noted during the last 2 weeks before the onset of labor (P less than 0.002). In IUGR, MSFT was significantly lower (P less than 0.001). In the cases of PROM and PD, MSFT was highly elevated (P less than 0.0001), independently of the gestational age. In pregnancies with well documented PMS, MSFT was much lower than in normal full term pregnancies with even a downward trend in serial determinations (P less than 0.0001).     

Detection of circulating trophoblast particles in maternal blood using density gradient centrifugation in preeclampsia and in normotensive pregnancies

Objective: Preeclampsia (PE) is a frequent pregnancy-related disease and a major cause of maternal and fetal morbidity and mortality. Despite that, exact mechanisms of its pathophysiology remain largely unknown. In pregnancies complicated by PE, changes in the regulation of apoptosis seem to result in increased apoptotic shedding of trophoblast particles (TPs) into maternal circulation. Since the number of TP in peripheral blood is low, their detection necessitates pre-analytical enrichment. Methods: In this prospective multicenter pilot study we aimed to analyze TP in peripheral blood of 29 women with PE and of 13 unaffected controls using the OncoQuick®plus system for cell enrichment. Using immunocytochemistry, slides were evaluated microscopically for TP. Statistical analyses were performed using Welch’s t-test or Fisher’s exact test. Results: TP were detected in 10 (34.5%) women with PE and in two (15.4%) of unaffected controls. More than one TP were only found in PE. Comparing the mean counts of TP between groups, we detected significantly more TP in PE (p = 0.046). Conclusions: The OncoQuick®plus system can be applied to detect TP in both women with PE and in normotensive pregnancies. Longitudinal studies investigating the role of TP as a screening method for patients at risk for PE are warranted.     

Maternal renal artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders.

Hypertensive disorders in pregnancy contribute to substantial maternal and perinatal morbidity and mortality. Clinically, these disorders are characterized by hypertension and proteinuria. However, these signs appear some time after the physiologic derangements have been initiated. The primary objectives of this study were as follows: 1) to establish baseline values for the maternal renal artery systolic-diastolic ratio (S/D) as a function of gestational age in normal pregnancies, and 2) to determine whether renal artery blood flow indices can accurately identify those pregnancies complicated by, or destined to develop, hypertensive disorders. Using a pulsed Doppler scanner, maternal renal artery duplex evaluation was performed in four groups of women: normotensive nonpregnant, normotensive pregnant, chronic hypertensive pregnant, and preeclamptic. In 30 normotensive pregnant women followed longitudinally, no change was noted in the renal artery S/D as gestational age advanced, with mean (+/- SD) values of 2.5 +/- 0.20 and 2.6 +/- 0.21 for the left and right sides, respectively. No clinically meaningful discriminations were detected when the four groups were compared. We conclude that maternal renal artery Doppler waveforms are not significantly altered by either pregnancy or hypertensive complications in pregnancy.     

Maternal angiogenic profile in pregnancies that remain normotensive

Objective

We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies.

Study design

Circulating levels of maternal placental like growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis.

Results

In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (p = 0.06) and second (p = 0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (p = 0.004) and second trimester (p = 0.008), but significantly lower sEng concentrations in both trimesters (p = 0.002 for first trimester and p = 0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p = 0.05 and p = 0.007, respectively) and second trimesters (p = 0.003 and p = 0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (r_s = 0.18, p = 0.03) and MAP (r_s = 0.16, p = 0.04). Second trimester sEng levels were inversely associated with second trimester MAP (r_s = −0.17, p = 0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics.

Conclusions

These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population.     

Maternal plasma alpha-fetoprotein in normal and complicated pregnancies.

Plasma alpha-fetoprotein (AFP) has been estimated by radioimmunoassay in healthy non-pregnant adults, some of whom were taking oral contraceptives, and in women with normal and complicated pregnancies. A curve with the 90 per cent range in normal pregnancy was established. The prop&rtion of values below the 5th centile in complicated pregnancies was significantly greater than in uncomplicated pregnancies. However, three-quarters of the estimations in the complicated groups lay within the 90 per cent range. Nor correlation was found between maternal plasma AFP values and the incidence of fetal distress, small-for-dates babies or perinatal mortality. It is concluded that the measurement of maternal plasma AFP is not reliable test for predicting fetal well-being.     

Maternal cytoglobin (CYGB) serum levels in normal and preeclamptic pregnancies

Objective: To investigate cytoglobin levels in women with preeclampsia and women with uncomplicated pregnancies.

Materials and methods: A cross-sectional study including 26 pregnant women complicated with early-onset preeclampsia (EO-PE) and 26 pregnant women complicated with late-onset preeclampsia (LO-PE) were recruited for the study group. Twenty-seven healthy pregnant women selected randomly were included in the control group. The serum CYGB concentrations were measured using an enzyme-linked immunosorbent assay.

Results: Gestational age at delivery and mean birth weight were significantly lower in the preeclampsia groups than in the control group and were found to be the lowest in the EO-PE group (p?p?p?=?1.000).

Conclusions: Serum CYGB levels were significantly higher in patients with EO-PE and LO-PE as compared to healthy pregnant women.     

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.     

Angiotensin II levels in hypertensive and normotensive pregnancies

We measured circulating angiotension II by radioimmunoassay in women with pregnancy-induced hypertension (n = 54), and compared these values with those obtained in women with normal pregnancy (n = 18) and in non pregnant women (n = 20). Pregnant women had statistically significantly higher plasma angiotensin II [mean (SD): 41.3 (12.6) pg/ml] than non-pregnant women [29.2 (11.3) pg/ml; P less than 0.004]. Angiotensin II concentrations in women with pregnancy-induced hypertension [mean (SD): 31.7 (16.2) pg/ml] were, on average, 25% lower than in normal pregnancy (P less than 0.003) and resembled those obtained in non-pregnant women. The lowest angiotensin II levels were found in women with more severe forms of pregnancy-induced hypertension, such as proteinuric or superimposed pregnancy-induced hypertension. Review of the published studies on angiotensin II and our data suggest that the conflict among studies on angiotensin II levels in pregnancy-induced hypertension is largely due to the heterogeneity of the study populations in the various reports.     

Angiotensin II levels in hypertensive and normotensive pregnancies

Summary. We measured circulating angiotension II by radioimmunoassay in women with pregnancy-induced hypertension (  n = 54  ), and compared these values with those obtained in women with normal pregnancy (  n = 18  ) and in non pregnant women (  n = 20  ). Pregnant women had statistically significantly higher plasma angiotensin II [mean (SD): 41.3 (12.6) pg/ml] than non-pregnant women [  29.2 (11.3) pg/ml; P < 0.004  ]. Angiotensin II concentrations in women with pregnancy- induced hypertension [mean (SD): 31.7 (16.2) pg/ml] were, on average, 25% lower than in normal pregnancy (   P < 0.003  ) and resembled those obtained in non-pregnant women. The lowest angiotensin II levels were found in women with more severe forms of pregnancy-induced hypertension, such as proteinuric or superimposed pregnancy-induced hypertension. Review of the published studies on angiotensin II and our data suggest that the conflict among studies on angiotensin II levels in pregnancy-induced hypertension is largely due to the heterogeneity of the study populations in the various reports.