Maternal plasma level of endothelin is increased in preeclampsia

Endothelin is a potent vasoconstrictor that is reportedly increased in conditions characterized by endothelial damage. Maternal plasma endothelin levels were compared between 27 women with preeclampsia (23 without and 4 with the hemolysis, elevated liver enzymes, and low platelet count syndrome) and 14 women with normotensive pregnancies. The mean +/- SEM plasma endothelin values were significantly higher in patients with preeclampsia uncomplicated by the hemolysis, elevated liver enzymes, and low platelet count syndrome (5.48 +/- 0.30 fmol/ml vs 3.86 +/- 0.28, p less than 0.001). In addition, the preeclamptic group with the hemolysis, elevated liver enzymes, and low platelet count syndrome had significantly higher endothelin levels than those without the syndrome (8.30 +/- 1.62 fmol/ml vs 5.48 +/- 0.30, p less than 0.05). There was no correlation between plasma endothelin values and either systolic or diastolic blood pressure. We conclude that plasma endothelin levels are significantly increased in women with preeclampsia and particularly in those with the hemolysis, elevated liver enzymes, and low platelet count syndrome, suggesting an association with widespread endothelial damage.     

Increased fetal DNA in the maternal circulation in early pregnancy is associated with an increased risk of preeclampsia

OBJECTIVE: The aim of our study was to determine if fetal DNA is present in the maternal circulation in early pregnancy before the clinical manifestation of preeclampsia, and if this could be predictive of the development of preeclampsia. STUDY DESIGN: Blood were obtained from patients attending for a first antenatal visit. Cases were asymptomatic women who subsequently developed preeclampsia matched to control women for parity and gestational age. Real-time polymerase chain reaction (PCR) using TaqMan primers and probes directed against SRY gene sequences quantified fetal DNA in the maternal circulation. RESULTS: There were 88 cases of women with preeclampsia and 176 control women, both sampled at a mean gestation (+/-SD) of 15.7 +/- 3.6 weeks. The presence of fetal DNA in the maternal circulation in early pregnancy is associated with an 8-fold increased risk of developing preeclampsia. CONCLUSION: Increased fetal DNA is present in the maternal circulation in early pregnancy in women who subsequently develop pre-eclampsia and there appears to be a graded response between the quantity of fetal DNA and the risk of developing pre-eclampsia.     

Calprotectin plasma level is elevated in preeclampsia

BACKGROUND: Calprotectin is a protein found in myelomonocytic cells and plays a role in various physiological functions such as inflammatory processes and antiproliferation of cells, and in the neutrophil defense against bacterial infections. Preeclampsia is characterized by maternal endothelial dysfunction and by insufficient trophoblast invasion into the maternal endometrium (decidua). In addition, preeclampsia is associated with maternal leukocyte activation and we therefore wanted to investigate whether calprotectin levels in plasma from women with preeclampsia differed from the levels in normotensive pregnant and nonpregnant women. METHOD: Calprotectin measurements were included in a case-control study of 20 preeclamptic women matched with 20 normotensive pregnant women regarding age, pregnancy length, parity and body mass index (BMI). We also measured calprotectin in 12 nonpregnant women. Calprotectin plasma levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We discovered significantly elevated plasma calprotectin levels in preeclamptic patients compared to matched normotensive pregnancies: 768 (612-1016) microg/L vs. 445 (276-598) microg/L (medians, 25, 75 percentiles, respectively), p = 0.002. CONCLUSIONS: The elevated plasma calprotectin levels demonstrated in the preeclampsia group supports the notion that leukocytes are activated in preeclampsia. The elevated calprotectin level might constitute a part of the innate defense in myelomonocytic cells against microorganisms in pregnancy. We suggest further elucidation of a role for calprotectin in the development of pregnancy disorders such as preeclampsia.     

Umbilical cord plasma leptin is increased in preeclampsia

OBJECTIVE: The objective of this study was to compare umbilical cord plasma leptin between infants of mothers who experienced preeclampsia and infants of control subjects and to study the relation between cord plasma leptin and infant obesity, as indicated by ponderal index. STUDY DESIGN: On the basis of a population of approximately 13,000 deliveries, we compared cord plasma leptin from preeclamptic (n = 256 women) and control pregnancies (n = 607 women) after taking the differences in gestational age and ponderal index into account. RESULTS: Cord plasma leptin increased strongly with gestational age, both in the preeclampsia group and the control subjects (P <.01), but at each gestational age the preeclampsia group had higher leptin levels than control subjects (P <.01). Adjustment for the higher ponderal index among control subjects (P <.05) did not alter the difference in leptin levels between the groups. CONCLUSION: We found higher levels of umbilical cord plasma leptin in infants of mothers who had preeclampsia (compared with infants of control subjects) after adjusting for differences in gestational age, gender, and infant ponderal index.     

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 CA-125 level is elevated in severe preeclampsia

AimThe aim of this study was to determine the relationship between serum concentrations of cancer antigen-125 (CA-125) and pre-eclampsia severity.MethodsWe evaluated 91 females with a singleton pregnancy. Serum CA-125 levels were measured in subjects with severe pre-eclampsia (n = 34) and those with mild pre-eclampsia (n = 24). Females with healthy pregnancies (n = 31) served as the control group. The three study groups were statistically similar in terms of maternal age, gestational age, and body mass index.ResultsThe CA-125 level was significantly higher in the severe pre-eclampsia group than that in the mild pre-eclampsia and control groups (p < 0.05). No significant difference in CA-125 levels between the mild pre-eclampsia and control groups was observed. CA-125 level was positively correlated with proteinuria (r = 0.489, p = 0.000), systolic blood pressure (r = 0.503, p = 0.018), and diastolic blood pressure (r = 0.532, p = 0.000). In contrast, CA-125 was negatively correlated with birth weight (r = 0.266, p = 0.012) and gestational age at birth (r = 0.250, p = 0.018).ConclusionsCA-125 level increased in severe pre-eclampsia, which reflected abnormal trophoblastic invasion and chronic inflammation. Elevated levels of CA-125 in pre-eclamptic patients may be a marker of the disease severity.     

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.     

Maternal periodontal disease is associated with an increased risk for preeclampsia

OBJECTIVE: To determine if maternal periodontal disease is associated with the development of preeclampsia. METHODS: A cohort of 1,115 healthy pregnant women were enrolled at less than 26 weeks' gestation and followed until delivery. Maternal demographic and medical data were collected. Periodontal examinations were performed at enrollment and within 48 hours of delivery to determine the presence of severe periodontal disease or periodontal disease progression. Preeclampsia was defined as blood pressure greater than 140/90 on two separate occasions, and at least 1+ proteinuria on catheterized urine specimen. The potential effects of maternal age, race, smoking, gestational age at delivery, and insurance status were analyzed, and adjusted odds ratios for preeclampsia were calculated using multivariable logistic regression. RESULTS: During the study period, 763 women delivered live infants and had data available for analysis. Thirty-nine women had preeclampsia. Women were at higher risk for preeclampsia if they had severe periodontal disease at delivery (adjusted odds ratio 2.4, 95% confidence interval 1.1, 5.3), or if they had periodontal disease progression during pregnancy (adjusted odds ratio 2.1, 95% confidence interval 1.0, 4.4). CONCLUSION: After adjusting for other risk factors, active maternal periodontal disease during pregnancy is associated with an increased risk for the development of preeclampsia.     

Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia

ObjectiveGhrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia.MethodThis retrospective case–control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated.ResultsThe ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34 ± 14.27 pg/mL vs 251.49 ± 16.15 pg/mL, P = 0.041, 1.07 ± 0.09 vs 0.82 ± 0.08, P = 0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35 ± 15.38 pg/mL vs 223.53 ± 18.61 pg/mL, P = 0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r = −0.549, P = 0.003; r = −0.491, P = 0.004) and was positively correlated with obestatin concentrations in preeclampsia (r = 0.388, P = 0.013).ConclusionsThe findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia.     

Nitric oxide production is not altered in preeclampsia

Background Preeclampsia remains a disease of theories as the real aetiology has remained elusive. Altered nitric oxide production has been associated with preeclampsia although conflicting results showing elevation, decrease or no change in nitric oxide levels have emerged from previous studies. Objective The aim of the study was to measure the serum levels of nitrate and nitrite in normal pregnancies and pregnancies complicated by pre-eclampsia. Materials and methods Venous blood was extracted from 39 normal pregnant women (control) and 34 women with preeclampsia (study group). Serum concentrations of nitrate and nitrite were determined using the HPLC method. Other special investigations including renal function tests were performed. The patients were managed according to protocol and the outcome of the pregnancies evaluated. Results There was no significant difference in the mean maternal age and gestational age at delivery between the groups. However the mean systolic and diastolic blood pressure of the study group (150.5 mmHg and 98.8 mmHg) were significantly higher than the levels in the control group, (110.86 and 85.5), p<0.0001. There was no significant difference in the mean serum nitrate levels (19.157±13.407 vs. 19.189±16.805) p=0.993. The fetal and maternal outcomes were comparable. Conclusion Our study has demonstrated that there was no alteration in nitric oxide production in preeclampsia, thus contributing to the existing unresolved role of nitric oxide in the pathogenesis of preeclampsia. Further research is called for.     

Maternal levels of growth differentiation factor-15 in patients with preeclampsia

ABSTRACT

Objective: Growth differentiation factor-15 (GDF-15) is a stress-induced cytokine and related to the prognosis of cardiovascular diseases. Our purpose is to measure the maternal levels of GDF-15 in patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE).

Methods: This cross-sectional study was conducted including 72 pregnant women, 23 with normal pregnancies and 49 with preeclampsia (26 with EOPE and 23 with LOPE). Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits.

Results: The median serum GDF-15 level was found to be the highest in the EOPE group (EOPE: 441.7 pg/ml). The median serum GDF-15 levels were higher in women with preeclampsia than in the control group (309.7 pg/ml vs. 436.6 pg/ml, p: 0.009).

Conclusion: Our findings suggest GDF-15 increased as a response to endothelial injury caused by cytokines triggered by preeclampsia.     

Analysis of plasma elastase levels in early and late onset preeclampsia

Background: Circulatory neutrophils have been reported to be activated in preeclampsia. It has been suggested that maternal plasma levels of elastase may serve as a possible cell-free marker to quantify such activation. Although plasma elastase levels have been found to be elevated in cases with manifest preeclampsia and eclampsia, this has not yet been examined in cases with early and late onset preeclampsia. We have now examined this aspect. Methods: In this retrospective study, maternal plasma samples were examined from eight cases with early onset preeclampsia (<34 weeks of gestation), eight cases with late onset preeclampsia (>34 weeks of gestation) and an equal number of gestational age matched normotensive term controls. Plasma concentrations of elastase were measured by ELISA using a commercially available assay. Results: Plasma elastase concentrations were significantly elevated the preeclampsia study group when compared to the normotensive control group (median=139.2 ng/ml versus median=72.1 ng/ml; P=0.0025). These elevations remained significant when the preeclampsia study group was stratified into case with early onset preeclampsia (median=118.8 ng/ml versus median=62.2 ng/ml; P=0.03), but jailed failed to attain significance for those cases with late onset preeclampsia (median=181.3 ng/ml versus median=86.3 ng/ml; P=0.061). Conclusions: Our data indicate that elastase levels are elevated in both early and late onset forms of preeclampsia, and imply that the activation of neutrophils may be more acute in the former than in the latter (238 words).     

母血中胎儿DNA与子痫前期关系的研究

目的:探讨孕妇外周血中胎儿DNA的浓度水平与子痫前期之间的关系。方法:留取第一次常规产前检查的472例孕妇的外周血并随访。设置阴性对照后,采用实时PCR方法定量检测怀男性单胎并发展为子痫前期的17例孕妇及34例怀男性单胎正常孕妇的血浆胎儿DNA的SRY基因浓度。结果:发展为子痫前期患者的外周血浆胎儿DNA浓度明显高于正常孕妇,中位数分别为165.41copies/ml和48.75copies/ml,有显著的统计学差异(P<0.001)。结论:发展为子痫前期患者外周血中的胎儿DNA明显增高,而浓度水平与子痫前期的严重程度似乎无关。     

Midregional pro-adrenomedullin plasma concentrations are blunted in severe preeclampsia

Levels of the peptide hormone adrenomedullin (AM) are elevated during normal pregnancy, but whether this differs during complications of pregnancy remains unresolved. AM can be quantified by measuring its pre-prohormone byproduct, midregional pro-adrenomedullin (MR-proADM). MR-proADM has shown prognostic value as a biomarker of heart failure, sepsis, and community-acquired pneumonia. Given the relevance of AM to pregnancy, we tested the hypothesis that MR-proADM provides a biomarker for preeclampsia. We find that MR-proADM plasma concentrations are blunted in severe preeclampsia and that MR-proADM is similarly effective as established biomarkers endoglin and placental growth factor at discriminating patients with severe preeclampsia from controls.     

Tumor necrosis factor-α is elevated in plasma and amniotic fluid of patients with severe preeclampsia

OBJECTIVE: Our purpose was to investigate whether markers for activation of the immune system are present in patients with preeclampsia by assessing maternal plasma and amniotic fluid for tumor necrosis factor-α and interleukin-1β. STUDY DESIGN: Twenty-one patients with severe preeclampsia composed the study group (group A). An antepartum comparison group was composed of healthy nulliparous patients not in labor and matched for gestational age (group B). Another control group consisted of term nulliparous patients in labor with uneventful pregnancies (group C). Maternal plasma samples were collected from all patients at recruitment and from patients in groups A and C immediately after delivery and again 20 to 24 hours post partum. Amniotic fluid was also collected from patients in groups A and C during labor. All samples were collectively assayed for tumor necrosis factor-α and interleukin-1β by specific enzyme-linked immunoassays. RESULTS: Before labor tumor necrosis factor-α was detected more frequently in the plasma of preeclamptic patients than in the plasma of patients in group B (12/16 vs 5/16, p < 0.05) and in higher concentrations (median 35 pg/ml vs median 0 pg/ml, p < 0.05). Although tumor necrosis factor-a was frequently detected in the plasma of patients in group C in early labor (16/20), concentrations were higher in the four preeclamptic patients first sampled in early labor (210 pg/ml vs 65 pg/ml, p < 0.05). Similarly, amniotic fluid levels of tumor necrosis factor-a were increased in preeclamptic patients compared with control patients. At delivery tumor necrosis factor-α was more likely to be identified in the plasma of preeclamptic patients and was found in higher concentrations, but by 20 to 24 hours post partum measurements in the preeclamptic and control patients were similar. There were no differences in the frequency with which interleukin-1β was detected or the concentration of interleukin-1β in any of the samples. CONCLUSIONS: Tumor necrosis factor-α is increased in the plasma and amniotic fluid of patients with severe preeclampsia. These data are suggestive of a role for abnormal immune activation in the pathophysiologic mechanisms of preeclampsia. (AM J Obstet Gynecol 1994;170:1752-9.)