Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia

INTRODUCTION: Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. METHODS: Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). RESULTS: The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). CONCLUSIONS: Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder.     

Macrophage migration inhibition factor is elevated in pregnancy, but not to a greater extent in preeclampsia

Background: Maternal serum concentrations of macrophage migration inhibitory factor (MIF) have recently been reported to be elevated in cases with preeclampsia. These findings may be important in increasing our understanding of the underlying events leading to the development of preeclampsia, as this cytokine is also expressed in the placenta, where it has been shown to possess immunemodulatory activities. For this reason we attempted to independently verify this report. Methods: Plasma levels of MIF were assessed by ELISA in plasma samples collected from normal healthy male and female blood donors (n=20 per group), as well as healthy normal pregnant women in all three trimesters of pregnancy (n=60). In addition, MIF levels were examined from cases with mild and severe preeclampsia (n=20 per study cohort) and matched normotensive pregnancies (n=20). Results: MIF levels were found to be elevated in pregnancy (median=10.1 ng/ml) when compared to non-pregnant controls (median=1.7 ng/ml). A moderate, but not significant, elevation was found to occur from the first to the third trimester of pregnancy. No significant difference was found to occur between the two preeclampsia study groups when compared to the normotensive control group. Conclusions: Our data suggest that circulatory MIF concentrations are elevated throughout pregnancy, but are not further increased in preeclampsia.     

Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia

OBJECTIVES: We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. METHODS: Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. RESULTS: Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (<34 weeks of gestation) and late (>34 weeks of gestation) onset preeclampsia. CONCLUSIONS: Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered.     

Utility of a Single Plasma Fibronectin Level for the Prediction of Preeclampsia

Previous studies have indicated that repeated maternal plasma fibronectin (FN) levels may aid in the prediction of preeclampsia. To investigate the development of a preeclampsia screening test, avoiding the requirement for repeated maternal blood samples throughout pregnancy, we examined the efficacy of a single screening plasma FN level for the prediction of preeclampsia. Total plasma FN levels were determined between 24 and 32 weeks' gestation in 115 normotensive patients, and cellular FN was determined in a subgroup of 81 of these patients. Among nulliparas (n = 76) total plasma FN values were significantly (P = 0.007) greater in patients (n = 13) who subsequently developed preeclampsia (median = 370, range 130-1104 μg/ml) than among those who remained nonpreeclamptic (median = 283, range 80-490 μg/ml). Based on maximization of the receiver/operator curve, a cut-off plasma FN value of 300 μg/ml was selected as a positive screen in the nulliparous group, resulting in a sensitivity of 85%, specificity of 60%, positive predictive value of 31% and a negative predictive value of 95%. Eleven of the thirteen nulliparous preeclamptics had positive plasma FN screens prior to onset of disease, with increased plasma FN occurring 8-14 weeks prior to the clinical onset of preeclampsia. There were no significant differences in cellular FN values between the nulliparous preeclamptics (median = 3.40, range 2.80–4-20 μg/ml) and nonpreeclamptics (median = 3.30, range 2.40-5.20 μg/ml; P = 0.41). Due to the low incidence of preeclampsia in the multiparous patients in our study (2.6%), measurements of neither total plasma nor cellular FN were found to be of value as a screening test in this group. These results indicate the potential value of a single maternal plasma FN screen at 24-32 weeks' gestation for predicting preeclampsia in nulliparous women.     

Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia

OBJECTIVE: The aim of our study was to determine if an elevated plasma homocysteine level in early pregnancy is associated with the development of severe preeclampsia. STUDY DESIGN: Blood samples were obtained from patients attending their first antenatal visit. Cases were asymptomatic women who subsequently developed severe preeclampsia. Controls were matched for gestational age and date of sample collection. Plasma homocysteine level was measured by using fluorescence polarization immunoassay. RESULTS: There were 56 patients with severe preeclampsia from whom blood samples were obtained at a mean (+/-SD) gestation of 15.3 weeks (+/-4.04 weeks) and 112 controls at 14.9 weeks (+/-3.41 weeks). The preeclampsia cases had a mean (+/-SD) homocysteine level of 9.8 micromol/L (+/-3.3 micromol/L), whereas controls had a mean homocysteine level of 8.4 micromol/L (+/-1.9 micromol/L), P < or = .0001. CONCLUSION: Women who develop severe preeclampsia have higher plasma homocysteine levels in early pregnancy than women who remain normotensive throughout pregnancy. An elevated plasma homocysteine level in early pregnancy can increase the risk of developing severe preeclampsia by almost threefold.     

Maternal serum anti-Müllerian hormone at 11–13 weeks’ gestation in the prediction of preeclampsia

Objective: To investigate the potential value of maternal serum anti-Müllerian hormone (AMH) at 11–13 weeks’ gestation in the prediction of preeclampsia (PE).

Methods: The serum concentration of AMH was measured at 11–13 weeks’ gestation in cases of PE (n?=?50) and normotensive controls (n?=?150). Backward stepwise multiple regression analysis was used to determine which of the factors amongst the maternal characteristics and gestation were significant predictors of the serum AMH in the control group and from the regression model the value in each case and control was expressed as a multiple of the expected median (MoM).

Results: In normotensive pregnancies, the maternal serum concentration of AMH is higher in Afro-Caribbean than in Caucasian women and in smokers than in non-smokers. In the PE group, the median serum concentration of AMH was significantly higher than in the controls (2.140?ng/L, IQR 1.968–2.273 versus 2.062?ng/L, IQR 1.938–2.181; p?=?0.025), but the median MoM value of AMH was not significantly different between the PE group and the controls (1.040, IQR 0.941–1.081 versus 0.995, IQR 0.939–1.065, p?=?0.147).

Conclusions: Maternal serum AMH is not an effective early predictor for PE.     

重度子痫前期临床发病类型及特点与围产结局的关系

目的探讨重度子痫前期临床发病类型和特点与围产结局的关系;进一步研究早发型重度子痫前期的临床界定及保守治疗的临床意义.方法173例重度子痫前期患者以孕34周发病时间为界,分为早发和晚发两种类型;再根据病程进展缓急（起病至发展为重度子痫前期＞48 h）进一步将其分为突发和渐进两种类型.共分4组：即早发突发型组10例、早发渐进型组87例、晚发突发型组18例、晚发渐进型组58例.对4组患者的一般临床资料、并发症发生情况、临床监测指标及围产结局进行分析比较.结果（1）早发突发型组及晚发突发型组共28例（16.2%）患者突发起病,病情于48 h内发展成重度子痫前期;早发渐进型组及晚发渐进型组共145例患者（83.4%）缓慢发病,病情于48 h后逐渐发展成重度子痫前期.早发突发型组的发生率与晚发突发型组比较,差异无统计学意义（P＞0.05）;早发渐进型组的发生率与晚发渐进型组比较,差异无统计学意义（P＞0.05）.（2）早发突发型组严重并发症发生率为100.0%（10/10）,早发渐进型组为34.5%（30/87）,晚发突发型组为100.0%（18/18）,晚发渐进型组为29.3%（17/58）.早发突发型组严重并发症发生率与早发渐进型组比较,差异有统计学意义（P＜0.001）;晚发突发型组严重并发症发生率与晚发渐进型组比较,差异有统计学意义（P＜0.001）.（3）早发突发型组胎（婴）儿死亡率为72.7%（8/11）,早发渐进型组为24.3%（25/103）,两组比较,差异有统计学意义（P＜0.01）.晚发突发型组胎（婴）儿死亡率为22.2%（4/18）,晚发渐进型组为4.9%（3/61）,两组比较,差异有统计学意义（P＜0.05）.（4）多因素回归分析显示,终止妊娠孕周是影响围产结局的主要因素;发病孕周以34孕周来界定早发和晚发类型时,发病孕周与围产结局无相关性（OR=0.426,95%CI：0.138～1.331）;以32孕周来界定早发和晚发类型时,则与围产结局相关（OR=0.177,95%CI：0.085～0.369）.结论重度子痫前期患者的临床发病类型较为复杂,早发突发型患者有临床上的不可预测性,其围产结局不良;晚发渐进型患者的围产结局较好.终止孕周是影响围产结局的主要因素,临床上以32孕周界定早发类型重度子痫前期更能准确反映发病孕周与围产结局的关系.     

Decreased Maternal Plasma Apelin Concentrations in Preeclampsia

Background. Preeclampsia is a hypertensive disorder that complicates 3–7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case–control study of pregnant women. Methods. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Results. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. <0.73 ng/mL) concentrations. Conclusion. Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders.     

Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia

OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic proteins placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1 (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia. METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1, PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early control group of women at 24-32 weeks of gestation, in a late control group of women at 36-42 weeks of gestation, and in cases of women with early-onset (before 32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia. RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had a three times higher median plasma sFlt1 level than late controls (P<.001). Women with early-onset preeclampsia had a 21 times lower median plasma PlGF level than early controls (P<.001). Women with late-onset preeclampsia had a five times lower median plasma PlGF level than late controls (P=.01). The median level of VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women. CONCLUSION: Both early- and late-onset preeclampsia are associated with altered plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early-onset rather than in late-onset disease.     

Relationship of maternal plasma leptin and risk of pre-eclampsia: a prospective study.

OBJECTIVE: We measured maternal plasma leptin concentrations in 55 women with pre-eclampsia and 487 normotensive women to determine whether elevated leptin concentrations were associated with the occurrence of pre-eclampsia. METHODS: Maternal blood samples were collected at 13 weeks' gestation, on average. Plasma leptin concentrations were determined using immunoassay. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Leptin concentrations were 78% higher in cases than control subjects (median 34.6 vs. 19.5 ng/ml; p < 0.001). Relative to women with leptin concentrations of < 27.4 ng/ml, those with elevated leptin concentrations (> or = 27.4 ng/ml) experienced a 2.3-fold increased risk of pre-eclampsia (OR 2.3; 95% CI 1.1-4.6). We observed evidence of a strong linear component of trend in risk of pre-eclampsia with increasing maternal plasma leptin concentration. Each 10-ng/ml increase in leptin concentration was associated with a 30% increase in pre-eclampsia risk (OR 1.3; 95% CI 1.1-1.5). Overweight women with elevated leptin concentrations experienced the highest risk of pre-eclampsia (OR 6.4; 95% CI 3.1-13.2) as compared with lean women with no leptin elevations. CONCLUSION: Elevated plasma leptin concentration and maternal overweight status appear to be independently associated with an increased risk of pre-eclampsia.     

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

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

Hyperhomocyst(e)inemia and elevated soluble vascular cell adhesion molecule-1 concentrations are associated with an increased risk of preeclampsia

Hyperhomocyst(e)inemia (HHcy) is a risk factor of endothelial dysfunction and preeclampsia. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, is elevated in preeclampsia. Few have assessed the joint contribution of these biomarkers in predicting preeclampsia. We assessed the extent to which HHcy and elevated sVCAM-1 are independently and jointly associated with preeclampsia. We conducted a case-control analysis of 100 preeclampsia cases and 100 controls to test our study hypothesis. Maternal plasma was collected before labor onset. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures. Plasma sVCAM-1 was determined using ELISA. Using the distribution of each analyte among controls, elevated tHcy was defined as plasma tHcy >6.6 micromol/l and elevated sVCAM-1 was defined as plasma concentrations >845 ng/ml (i.e., values above the median). Odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Compared with women without elevated tHcy and without elevated sVCAM-1 (the referent group), those with elevated sVCAM-1 alone had a 4.1-fold increased risk of preeclampsia (95% CI 1.2-13.8). The OR for women with elevated tHcy alone was 2.2 (95% CI 0.6-7.9). The OR for women with elevated tHcy and sVCAM-1 was 13.2 (95% CI 4.1-42.2). Elevated tHcy and sVCAM-1 together were strongly associated with an increased risk of preeclampsia. Larger, prospective studies are needed to confirm these findings and to determine the extent to which elevated tHcy and sVCAM-1 together in early pregnancy are predictive of preeclampsia risk.     

Plasma homocyst(e)ine concentrations in eclamptic and preeclamptic African women postpartum.

OBJECTIVE: To examine the relationship between plasma homocyst(e)ine and risk of eclampsia and preeclampsia among sub-Saharan African women who delivered at Harare Maternity Hospital in Zimbabwe. METHODS: We ran a hospital-based, case-control study at Harare Maternity Hospital, University of Zimbabwe, Harare, Zimbabwe comprising 33 pregnant women with eclampsia and 138 with preeclampsia. Controls were 185 normotensive pregnant women. Plasma was collected postpartum and homocyst(e)ine levels were measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Women with eclampsia or preeclampsia had significantly higher mean homocyst(e)ine levels than normotensive controls (12.54 or 12.77 micromol/L versus 9.93 micromol/L, respectively, P<.001). The odds ratio (OR) for eclampsia was 6.03 among women in the highest quartile of the control homocyst(e)ine distribution (median 13.9 micromol/L) compared with women in the lowest quartile (median 6.2 micromol/L). The corresponding OR for preeclampsia was 4.57. Nulliparas with elevated homocyst(e)ine had a 12.90 times higher risk of preeclampsia compared with multiparas without elevated homocyst(e)ine. CONCLUSION: Postpartum plasma homocyst(e)ine concentrations are higher among Zimbabwean women with eclampsia and preeclampsia compared with normotensive women.     

子(癎)前期孕妇中性粒细胞相关因子与胎儿的关系

目的:了解中性粒细胞在子前期胎儿中的状态,探讨其在胎儿患病中的作用。方法:采用流式细胞术检测20例子前期患者和20例正常妊娠孕妇肘静脉血和脐静脉血中中性粒细胞粘附分子CD11b的表达,同时采用酶联免疫吸附实验检测两组血浆IL-8和弹性蛋白酶的浓度。结果:①子前期组母体静脉血CD11b的平均对数荧光强度指数、血浆IL-8和弹性蛋白酶的浓度均高于正常妊娠组(P<0.05);②子前期组脐静脉血CD11b的平均对数荧光强度指数高于正常妊娠组(P<0.05),但血浆IL-8和弹性蛋白酶的浓度与正常妊娠组比较无统计学差异(P>0.05);③胎儿脐静脉血中的中性粒细胞CD11b平均对数荧光强度指数与母体静脉血中的中性粒细胞CD11b平均对数荧光强度指数有正相关关系(r=0.590,P<0.01)。结论:子前期胎儿中性粒细胞的激活与母体中性粒细胞的激活相关,胎儿循环中存在中性粒细胞的激活,推测中性粒细胞在子前期胎儿病率中有一定作用。     

Maternal plasma-soluble ST2 concentrations are elevated prior to the development of early and late onset preeclampsia – a longitudinal study

Objective: The objectives of this study were to determine (1) the longitudinal profile of plasma soluble ST2 (sST2) concentrations in patients with preeclampsia and those with uncomplicated pregnancies; (2) whether the changes in sST2 occur prior to the diagnosis of preeclampsia; and (3) the longitudinal sST2 profile of women with early or late preeclampsia.

Materials and methods: This longitudinal nested case–control study included singleton pregnancies in the following groups: (1) uncomplicated pregnancies (n?=?160); and (2) those complicated by early (<34 weeks, n?=?9) and late (≥34 weeks, n?=?31) preeclampsia. sST2 concentrations were determined by enzyme-linked immunosorbent assays. Mixed-effects models were used for the longitudinal analysis.

Results: (1) Plasma sST2 concentration profiles across gestation differed significantly among cases and controls (p?22 weeks of gestation; cases with late preeclampsia had higher mean concentrations at >33 weeks of gestation (both p?Conclusions: Maternal plasma sST2 concentrations are elevated 6 weeks prior to the clinical diagnosis of preeclampsia. An increase in the maternal plasma concentration of sST2 may contribute to an exaggerated intravascular inflammatory response and/or the Th1/Th2 imbalance in some cases.     

Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia

OBJECTIVE: Elevated amounts of circulating fetal deoxyribonucleic acid in maternal plasma have recently been detected in pregnancies complicated by preeclampsia. We attempted to confirm this finding and simultaneously examined the quantity of maternal circulating deoxyribonucleic acid. STUDY DESIGN: Circulating deoxyribonucleic acid was measured by realtime quantitative polymerase chain reaction in plasma samples obtained from 44 women with preeclampsia and a matched cohort of 53 normotensive pregnant women. RESULTS: We confirmed that circulating fetal deoxyribonucleic acid levels were significantly elevated in pregnancies complicated by preeclampsia (3194.6 vs 332.8 copies/mL; P < .001). We also showed for the first time that circulating maternal deoxyribonucleic acid levels are also elevated (219,023.9 vs 20,235.8 copies/mL; P < .001). The increases in these deoxyribonucleic acid levels corresponded to the severity of the disorder, and values were correlated with each other in pregnancies complicated by preeclampsia (r = 0.556; P < .001) but not normotensive pregnancies (r = 0.046; P = .747). CONCLUSION: The releases of both free fetal and maternal deoxyribonucleic acid were found to be affected in preeclampsia.     

Comparison of maternal serum total activin A and inhibin A in normal, preeclamptic, and nonproteinuric gestationally hypertensive pregnancies.

OBJECTIVE: The aim of the study was to compare maternal serum levels of activin A and inhibin A in pregnancy complicated by preeclampsia, pregnancy complicated by gestational hypertension, and normal pregnancy from 25 to 42 weeks' gestation. STUDY DESIGN: Activin A and inhibin A levels were measured by 2-site enzyme-linked immunosorbent assay in 60 subjects with preeclampsia, 60 control normotensive pregnant women matched for gestational age, and 51 unmatched subjects with gestational hypertension. RESULTS: Activin A levels were higher in the preeclampsia group (median 31.5 ng/mL and interquartile range 10.5 ng/mL) than in the control group (median 10.6 ng/mL and interquartile range 9.5 ng/mL, P <.0001) and the gestational hypertension group (median 21.4 ng/mL and interquartile range 15.2 ng/mL, P <.003). Inhibin A levels were greater in the preeclampsia group (median 1833 pg/mL and interquartile range 1464 pg/mL) than in control subjects (median 698 pg/mL and interquartile range 583 pg/mL, P <.0001). Control levels were significantly related to gestational age. CONCLUSIONS: Levels of both analytes were greater in preeclampsia and activin A levels were greater in gestational hypertension than in normotensive pregnancy. These analytes may prove to be clinically useful laboratory markers for preeclampsia.     

Maternal plasma vascular endothelial growth factor concentrations in normal and hypertensive pregnancies and their relationship to peripheral vascular resistance

OBJECTIVE: The aim of this study was to measure maternal plasma vascular endothelial growth factor concentrations during normal and hypertensive pregnancies and examine their relationship with maternal total peripheral resistance values. STUDY DESIGN: Plasma concentrations of total immunoreactive vascular endothelial growth factor and total peripheral resistances were measured serially throughout pregnancy in 20 women with preeclampsia, 24 women with gestational hypertension, and 26 normotensive control women. One-way analysis of variance and a regression model were used to analyze the vascular endothelial growth factor levels in the groups and the relationship between vascular endothelial growth factor concentration and total peripheral resistance. RESULTS: At 10 to 14 weeks' gestation plasma vascular endothelial growth factor concentrations in all subjects were 4 to 5 times greater than the levels measured post partum (P <.0001). Mean vascular endothelial growth factor concentrations were similar in the control and gestational hypertension groups; in both groups levels remained stable until 34 to 36 weeks' gestation, when levels increased a further 1.3-fold (P <.01). In comparison, vascular endothelial growth factor concentrations in subjects in the preeclampsia group were greater at 28 to 32 weeks' gestation (P =.002) and at 34 to 36 weeks' gestation (P <.001). Vascular endothelial growth factor concentrations were also increased during the 4 weeks that preceded the diagnosis of preeclampsia (P <.05). Vascular endothelial growth factor concentrations were associated with the elevated total peripheral resistance observed during the clinical disorder in the preeclampsia group but not in the other groups. CONCLUSION: Maternal plasma vascular endothelial growth factor concentrations increased before the clinical onset of preeclampsia and were further elevated during the vasoconstricted state observed in this disorder. We speculate that the hyperdynamic circulation that characterizes the latent phase of preeclampsia causes vascular shear stress, which in turn increases the levels of circulating vascular endothelial growth factor. Because vascular endothelial growth factor normally acts as a vasodilator, its increase may represent an unsuccessful vascular rescue response.     

Placenta growth factor is not an early marker for the development of severe preeclampsia

OBJECTIVE: Our purpose was to determine whether plasma concentrations of placenta growth factor may be used as a marker for women who ultimately have severe preeclampsia. STUDY DESIGN: We performed a nested case-control study to compare plasma concentrations of placenta growth factor in women with severe preeclampsia with the concentrations in normotensive pregnant control subjects. Plasma samples were collected at <20 weeks' gestation and again in the third trimester. Twenty-two women who ultimately had severe preeclampsia were matched for gestational age at delivery with 22 normotensive control subjects. Placenta growth factor concentrations were measured by a specific antigen capture enzyme-linked immunosorbent assay. Comparisons were made by using the Mann-Whitney U test for nonparametric data such as placenta growth factor concentrations. The Student t test was used for parametric data. RESULTS: A total of 880 pregnant women were screened. Severe preeclampsia developed in 22, for an incidence of 2.5%. As expected, women with severe preeclampsia had significantly higher systolic and diastolic blood pressures, and their infants had lower birth weights. Placental weights at delivery were similar between those with severe preeclampsia and control subjects (659 vs 699 g; P =.51). During the third trimester, the median placenta growth factor concentrations were significantly lower in women with severe preeclampsia than in normotensive control subjects (125 vs 449 pg/mL; P =.003). When samples drawn at <20 weeks' gestation were compared, there was no difference between the group with severe preeclampsia and those who remained normotensive (98.8 vs 56.34 pg/mL; P =.15). CONCLUSION: During the third trimester, patients with severe preeclampsia have decreased maternal concentrations of placenta growth factor. This difference is not seen earlier in pregnancy. Lower concentrations of placenta growth factor may be a result of severe preeclampsia rather than a causal factor. Placenta growth factor is not a good marker for the subsequent development of severe preeclampsia.     

Adrenomedullin levels in normal and preeclamptic pregnancy at term

OBJECTIVE: To describe maternal plasma levels of adrenomedullin (AM), a hypotensive and natriuretic peptide, in normal and preeclamptic women at term. STUDY DESIGN: Maternal plasma AM levels were determined in 13 preeclamptic and 15 normotensive primigravidas by radioimmunoassay. Plasma samples were obtained with the patients in the lateral recumbent position before the administration of any medications. RESULTS: Women with preeclampsia had significantly elevated AM levels when compared with normotensive controls (42.3 +/- 10.5 pg/mL versus 16.9 +/- 3.1 pg/mL, P < .011). CONCLUSION: In this pilot study, AM levels were significantly increased at term in preeclamptic women.