Changes in serum levels of heat shock protein 70 in preterm delivery and pre-eclampsia

AIM: The aim of this study was to investigate heat-shock protein (Hsp)70 as a novel marker to evaluate the curative effects of treatment for preterm delivery high-risk patients and pre-eclampsia. METHODS: After obtaining informed consent, serum samples were collected from 31 preterm delivery high-risk patients with a tocolysis index of three points or above (A), seven pre-eclampsia patients (P), 46 normal pregnant women (B), and seven non-pregnant women (C). Of the 31 preterm delivery high-risk patients, 15 had preterm delivery (Ap) and 16 had full-term delivery (Af). The levels of Hsp70 were measured using enzyme-linked immunosorbent assay. RESULTS: The Hsp70 levels in normal pregnant women were 8.6 +/- 1.9 ng/mL (first trimester), 5.5 +/- 1.0 ng/mL (second trimester) and 5.5 +/- 0.7 ng/mL (third trimester). There was no statistical difference in the Hsp70 levels between the three trimesters. The mean Hsp70 levels were 21.9 +/- 5.3 ng/mL (A), 35.3 +/- 9.6 ng/mL (Ap), 9.4 +/- 2.2 ng/mL (Af), 24.4 +/- 3.6 ng/mL (P), 6.1 +/- 0.6 ng/mL (B), and 2.4 +/- 0.6 ng/mL (C). Group Ap had significantly higher Hsp70 levels than group Af (P = 0.0112) and group B (P <0.0001). The duration of pregnancy after hospitalization for group Ap was significantly shorter than that for group Af (P=0.0088) and group B (P <0.0001). Group P also had significantly higher Hsp70 levels than group B (P <0.0001). CONCLUSION: Because Hsp70 levels were particularly high in treatment-resistant preterm delivery cases, Hsp70 may prove to be a useful marker for evaluating the curative effects of treatment for preterm delivery.     

Evaluation of natural coagulation inhibitor levels in various hypertensive states of pregnancy

OBJECTIVE: To evaluate the role of natural coagulation inhibitors in various classifications of pregnancy associated hypertension in Turkish population living in Trakya region of Turkey. STUDY DESIGN: Serum uric acid levels, plasma protein C (PC), protein S (PS), antithrombin III (AT III) activities and activated protein C resistance (APCR) were measured in 80 pregnant women with hypertension (preeclampsia, n = 32; severe preeclampsia, n = 25; eclampsia, n = 14; chronic hypertension, n = 9) and 58 healthy pregnant women. Tukey and Tamhane multiple comparison tests, Kruskal-Wallis, chi2 and Fisher's exact tests were performed for comparison of means and/or medians. RESULTS: Serum uric acid levels were significantly elevated in women with preeclampsia and severe preeclampsia, but PS activity decreased in women with severe preeclampsia (33.2 +/- 18.9% versus 50.4 +/- 22.7%, p = 0.015) and chronic hypertension (29.5 +/- 14.5% versus 50.4+ /- 22.7%, p = 0.045) compared to healthy controls. There was no significant difference in APCR, and PC or AT III activity between the groups. Platelet counts were significantly lower in women with severe preeclampsia, compared to controls and women with chronic hypertension. CONCLUSION(S): Serum uric acid levels and plasma protein S activity may be useful as indices of severity of pathology in pregnancy associated hypertension.     

Soluble Flt-1 as a diagnostic marker of pre-eclampsia

BACKGROUND: Serum levels of soluble fms-like tyrosine kinase (sFlt-1) increase in pre-eclampsia (PE). Aims: To determine whether concentrations of serum sFlt-1 can differentiate PE or superimposed PE (SPE) from gestational hypertension (GH) or chronic hypertension (CH). METHODS: Blood was collected from pregnant women being investigated for hypertension (blood pressure of > 140 and/or 90 mmHg). Normotensive (NP) and pre-eclamptic (PE-C) control ranges were measured. RESULTS: Patients with evolving hypertension in pregnancy eventually fell into four groups: GH (n = 14), PE (n = 7), CH (n = 9) and SPE (n = 9). Patients who later developed pre-eclampsia had a higher sFlt-1 (PE: 2.61 ng/mL and SPE: 2.77 ng/mL, respectively) than GH (P < 0.001) or CH (1.05 ng/mL, P = 0.11). Women with established PE at recruitment (PE-C; (n = 18) (3.13 ng/mL; interquartile range (IQR): 2.14-4.17 ng/mL) had a median sFlt-1 higher than NP (n = 18) (0.47 ng/mL; IQR: 0.11-0.89) (P < 0.0008). Patients with GH compared to NP had a slight increase (1.33 ng/mL, P < 0.003). Using a sFlt-1 cut-off of > or = 1.9 ng/mL yielded a sensitivity of 94% (95% confidence interval (CI) 73-100%) and specificity of 78% (95% CI 64-82%). CONCLUSIONS: sFlt-1 was elevated in women with PE compared to NP. The sFlt-1 also differentiated women destined to develop PE among those who presented with a diagnostic rise in maternal blood pressure. The sFlt-1 test is a useful diagnostic test for PE.     

Thrombophilic syndrome associated to phenotypic resistance to activated protein C in postmenopausal women

AIM: Hormone replacement therapy (HRT) may reduce the risk of cardiovascular events in healthy postmenopausal women. However recent studies suggest a 2-4 fold increased risk of idiopathic venous thromboembolism (VTE) among users of HRT. Our aim was to evaluate the overall effect of HRT on hemostatic variables probably related to increased VTE risk reported in epidemiological studies. METHODS: Therefore, 100 healthy postmenopausal women aged 45-60 years divided into 50 HRT non-users and 50 HRT users were examined. The authors assayed on the automated coagulometer ACL7000 (Instrumentation Laboratory, Milan) the procoagulant proteins: factor VIII (VIII:C) and factor VII (VII:C); the natural anticoagulant proteins: antithrombin (ATIII), protein C (PC), protein S (PS) and the resistance to anticoagulant action of activated protein C (APC-Resistance). The free tissue factor pathway inhibitor (TFPI) was measured with an ELISA method (Diagnostica Stagò; France, Roche). The in vivo coagulation and fibrinolysis activation was evaluated by the assays of prothrombin fragment 1+2 (F1+2) and plasmin- antiplasmin complexes (PAP) using ELISA techniques. RESULTS: Increased levels of FVIII:C and FVII:C were observed in HRT users and HRT non-users women compared to controls (FVIII:C= 126+/-58%, 120+/-59% vs 85+/-15% p=0.0001; FVII: C 113+/-23%, 103+/-19% vs 90+/-16% p=0.0001). The activation peptides were significantly different compared to those found in control subjects; higher values were observed in HRT users compared to HRT non-users (F1+2=1.11+/-0.44 nM, 077+/-0.31 nM vs 0.45+/-0.35 p=0.00001; P-AP= 606+/-406 ng/ml, 514+/-205 ng/ml vs 235+/-59 p=0.0001). The ATIII and the PC were similar among the 3 different groups of subjects, but reduced levels of PS were observed in HRT users (PS 93+/-23%, 105+/-22% vs 109+/-12 p=0.0001). The mean normalized APC sensitivity ratio (APC-SR) was lower in the two populations of women as compared with that of controls (nAPC-SR 1.02+/-0.7, 1.02+/-0.8 vs 1.1+/-25 p=0.02). The values of free TFPI were reduced in HRT users compared to HRT non-users (9.1+/-1.9 ng/ml, 10.1+/-2.3 ng/ml vs 4.6+/-1.5 ng/ml p<0.0001). CONCLUSION: HRT appears to be associated to a shift in the procoagulant-anticoagulant balance towards a procoagulant state. The changes in hemostatic system could explain the increased risk of VTE in healthy postmenopausal women during HRT, nevertheless this risk could be higher in women known to have a congenital or acquired thrombophilic state.     

Serum advanced oxidation protein products, myeloperoxidase and ascorbic acid in pre-eclampsia and eclampsia

BACKGROUND: Activation products from neutrophils and the complement system might cause endothelial dysfunction, which is central to the aetiology of pre-eclampsia. This study aimed to investigate the activity of myeloperoxidase (MPO), and its association with advanced oxidation protein products (AOPP), in women with pre-eclampsia and eclampsia. MATERIALS AND METHOD: Twenty-one pregnant women with pre-eclampsia, 11 pregnant women with eclampsia and 19 healthy pregnant women were studied. Serum levels of malondialdehyde (MDA), AOPP, ascorbic acid (AA) and activities of MPO and catalase (CAT) were measured using a colorimetric method. RESULTS: The MDA level was significantly higher in the pre-eclampsia (3.15+/-0.28 nmol/mL) and eclampsia (4.01+/-0.66 nmol/mL) groups than in controls (1.85+/-0.18 nmol/mL); the difference between MDA levels in the pre-eclampsia and eclampsia groups was not statistically significant. MPO activity was significantly higher in the eclampsia (347.59+/-88.06 U/L) group than in the pre-eclampsia (196.17+/-30.8) and control (93.22+/-9.52) groups, and there was also no significant difference in these levels between the pre-eclampsia and control groups. CAT activity was significantly higher in the pre-eclampsia (166.35+/-31.75 U/L) and eclampsia (166.98+/-40.31 U/L) groups than in controls (81.28+/-7.41 U/L), and AA level was significantly higher in the pre-eclampsia (0.54+/-0.15 mg/dL) group than in controls (0.18+/-0.01 mg/dL); the differences in AA and CAT activity between the pre-eclampsia and eclampsia groups were not statistically significant. AOPP levels did not change significantly among the control, pre-eclampsia and eclampsia groups (106.88+/-5.62, 98.89+/-6.47, 111.89+/-6.8 micromol/L, respectively). CONCLUSIONS: We suggest that increased oxidative stress might contribute to the pathophysiological mechanisms of pre-eclampsia and eclampsia, and that AA and CAT might have a protective role via free radical-scavenging properties. However, further study is needed.     

Elevated C-reactive protein and pro-inflammatory cytokines in Andean women with pre-eclampsia.

OBJECTIVE: To investigate the concentration of markers of inflammation in non-pregnant women, women with normal pregnancy and women with pre-eclampsia. METHODS: Pregnant women (n=26), women with pre-eclampsia (n=25) and non-pregnant normotensive women (n=21) were included in the study. C-reactive protein was measured by latex-enhanced immunoturbidimetric assay, serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by high sensitivity ELISA. Kruskal-Wallis non-parametric analysis of variance followed by the Mann-Whitney U-test were used for statistical analyses. RESULTS: Higher values (mean+/-S.E.M.) of C-reactive protein were found in pre-eclampsia (4.11+/-0.37 mg/dl) compared with normal pregnant women (2.49+/-0.26 mg/dl) and non-pregnant controls (1.33+/-0.15 mg/dl). TNF-alpha was significantly higher in women with pre-eclampsia (15.74+/-5.09 pg/ml), in relation to the control group (2.76+/-0.41 pg/ml) and women with normal pregnancy (8.31+/-1.55 pg/ml). IL-6 levels were significantly higher in pre-eclamptic women (12.91+/-1.29 pg/ml) compared with normal pregnant (5.07+/-0.423 pg/ml) and control women (1.25+/-0.13 pg/ml). CONCLUSIONS: The results of this cross-sectional study in a high-risk Andean population show that both C-reactive protein and pro-inflammatory cytokines are present in higher concentrations in women with pre-eclampsia. The study was undertaken in women with established pre-eclampsia and it is not possible to determine whether the increased concentrations of C-reactive protein and pro-inflammatory cytokines were a cause or consequence of the disease.     

辅助性T淋巴细胞1和2比率变化与妊娠期高血压疾病发病的关系

目的探讨辅助性T淋巴细胞(Th)1、2比率变化与妊娠期高血压疾病发病的关系。方法采用流式细胞技术,分别检测12例正常未妊娠妇女(正常未孕组)、12例正常妊娠妇女(正常妊娠组)、10例妊娠期高血压患者(高血压组)、25例子痫前期患者(包括10例轻度和15例重度,子痫前期组)的外周血及蜕膜组织(正常未孕组除外)中的Th1/Th2比率。结果正常未孕组妇女外周血中的Th1/Th2比率为10.5±1.5,正常妊娠组妇女外周血及蜕膜组织中的Th1/Th2比率分别为9.5±2.9及7.6±4.6、高血压组妇女分别为12.1±3.4及13.1±5.6、子痫前期组分别为16.8±3.8及26.7±9.4。子痫前期组外周血及蜕膜组织中Th1/Th2比率均明显高于其他各组,分别比较,差异均有统计学意义(P<0.05);且子痫前期组蜕膜组织中Th1/Th2比率明显高于外周血,两者比较,差异有统计学意义(P<0.001)。高血压组妇女的Th1/Th2比率变化处于子痫前期组和正常妊娠组之间。结论妊娠期高血压疾病患者Th1/Th2比率升高,导致Th1/Th2比率平衡紊乱可能是妊娠期高血压疾病发生的重要原因。     

Selective deficit of angiogenic growth factors characterises pregnancies complicated by pre-eclampsia.

OBJECTIVE: To compare serum levels of angiogenic growth factors vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and angiogenin in pre-eclamptic women and matched controls. DESIGN: Retrospective analysis of -70 degrees C stored serum of women who developed pre-eclampsia and matched controls. SETTING: Department of Gynaecology and Obstetrics, St Elisabeth Hospital, Cura?ao, Netherlands Antilles. SAMPLE: Thirty women with pre-eclampsia and 30 normotensive controls matched for age and gestation. RESULTS: VEGF and PIGF serum levels were significantly lower in pre-eclamptic pregnancies, compared with controls (VEGF 0.31 +/- 1.20 vs 18.30 +/- 24.97 pg/mL, P = 0.0004; PlGF 54.19 +/- 32.05 vs 497.95 +/- 340.51 pg/mL, P < 0.0001). Matched couple analysis showed VEGF serum concentrations to be lower in the majority of pre-eclamptic women and PlGF concentrations to be lower in all pre-eclamptic women. Angiogenin serum levels showed no statistical significant difference between pre-eclamptic pregnancies and controls (523.68 +/- 367.55 vs 670.41 +/- 251.54 ng/mL, P = 0.058), with matched couple analysis showing no clear pattern. CONCLUSIONS: Decreased serum levels of VEGF and PIGF characterise, and therefore seem to be of importance during (the development of), pre-eclampsia. This selective deficit of angiogenic growth factors might in part explain the shallow placentation found in this pregnancy complication.     

Serum adiponectin levels in normal and hypertensive pregnancy.

OBJECTIVE: The aim of this study was to quantify adiponectin levels in women with normal and hypertensive pregnancies to determine whether there is an independent association, while controlling for body fat and insulin sensitivity. METHODS: A cross-sectional study was conducted in the following categories: 12 normotensive non-pregnant women, 10 normotensive, 12 gestational hypertensive, 13 essential hypertensive, and 12 preeclamptic women. All subjects underwent measurements of body fat by bio-impedance analysis and blood sampling. RESULTS: Percentage of body fat and insulin resistance were greater in all pregnant groups compared with non-pregnant women. Adiponectin concentrations were significantly lower in women with normal pregnancies (18.6 +/- 1.4 microg/mL, p = 0.02) compared with non-pregnant women (24.0 +/- 1.5 microg/mL). However, adiponectin levels were not significantly different among normal pregnancy, gestational hypertension (19.0 +/- 3.1 microg/mL), essential hypertension (24.0 +/- 3.7 microg/mL) and pre-eclampsia (22.4 +/- 2.5 microg/mL) groups. Adiponectin levels were inversely related to percent body fat and insulin resistance. When adiponectin levels were corrected for percent body fat and insulin resistance, no significant differences were seen among the study groups. CONCLUSIONS: Adiponectin levels are decreased in normal pregnancy, however this difference disappears when adiponectin levels are corrected for the pregnancy-related increases in body fat and insulin resistance. Adiponectin levels are not altered significantly in states of hypertension in pregnancy compared with normal pregnancy.     

Elevated serum uric acid levels in gestational hypertension are correlated with insulin resistance

The purpose of this study was to assess a possible correlation between insulin resistance and uric acid levels in gestational hypertension (GH) and preeclampsia. Fourteen pregnant, nondiabetic women with either GH (n = 7) or preeclampsia (n = 7) and nine pregnant healthy controls in the third trimester were enrolled onto the study. Fasting serum was collected and insulin sensitivity was determined by Homeostasis Model Assessment based on the algorithm developed by Turner and colleagues. Serum samples were also analyzed for creatinine and uric acid levels. Insulin resistance and uric acid levels were compared between hypertensive and control pregnant women, and the association between these two variables was calculated. There were no significant differences in mean age, weight, body mass index, and glucose challenge test between all hypertensive patients and controls. Significant differences were revealed in insulin sensitivity between hypertensive and nonhypertensive pregnant women (45 +/- 31.2% vs. 79.7 +/- 33%; p = 0.018). In our study, uric acid levels were not significantly higher for hypertensive patients (5.46 +/- 0.85 vs. 4.53 +/- 1.4 mg/dL in controls; p = 0.06). The elevated serum uric acid levels were highly correlated to insulin resistance in patients with GH. In contrast, uric acid levels did not correlate with insulin sensitivity in patients with preeclampsia and controls. Insulin resistance is associated with the elevated uric acid levels found in nonproteinuric gestational hypertensive disease.     

Platelet sensitivity to prostaglandin E1 inhibition is reduced in pre-eclampsia but not in nonproteinuric gestational hypertension

Objective Platelet aggregometry was used to discriminate platelet sensitivity to prostaglandin E, (PGE.) inhibition, to evaluate whether platelet behaviour in pre-eclamptic women was different in this respect than from that in nonproteinuric hypertensive women.
Methods The amount of PGE₁ required to inhibit in vitro platelet aggregation induced by arachidonic acid was determined in samples from 60 women: 20 nonpregnant controls, 20 women with normal pregnancies, 10 women with gestational hypertension and 10 with pre-eclampsia.
Results The response to arachidonic acid was similar among the four groups. Amounts of PGE₁ necessary to inhibit platelet aggregation were significantly higher in normal pregnant women compared with nonpregnant controls (   P < 0.001  ). Platelets from pre-eclamptic women required significantly higher concentrations of PGE, to inhibit aggregation than the other groups studied (   P < 0.001  ). However, there was no significant difference between normal and nonproteinuric hypertensive pregnant women.
Conclusions Our findings support the notion that increased platelet reactivity during late pregnancy is exacerbated in pre-eclamptic women but not in nonproteinuric hypertensive women. This is in agreement with the hypothesis that pre-eclampsia and gestational hypertension are different conditions. Prospective studies are required to confirm if this simple test may be useful in the early identification of pregnant women at risk for pre-eclampsia.     

A study of alpha-human atrial natriuretic peptide in normal pregnancy and in pre-eclampsia.

The object of this study was to compare plasma levels of alpha-human atrial natriuretic peptide (ANP) in patients with pre-eclampsia, normal pregnant women, and healthy non-pregnant women. This was an observational study carried out at Llandough Hospital, Cardiff, Wales on 85 age-matched women divided into three groups (30 patients with pre-eclampsia, 30 healthy pregnant women in the third trimester and 25 healthy non-pregnant women). Plasma ANP concentration was measured between 14.00 and 16.00 hours, in the recumbent position using pre-extraction radioimmunoassay. The following measurements were also performed: blood urea, serum creatinine, serum uric acid and serum sodium in all study subjects and 24-hour urinary protein in pregnant women. All women were eating a normal diet. It was shown that plasma ANP levels were significantly higher in healthy pregnant women in the third trimester of pregnancy than in non-pregnant women (18.12 +/- 7.36 vs. 13.68 +/- 6.41 pmol/l, P < 0.05). This difference was also observed in pre-eclamptic women (17.6 +/- 12.06 pmol/l vs. 13.68 +/- 6.41 pmol/l, P < 0.05) but the plasma hormone levels were not significantly different from healthy pregnant women. In all pregnant women, plasma ANP level was related to the gestational age and birth weight as shown by the regression coefficient (+ 0.39,-0.26 respectively, P < 0.05). In pre-eclamptic patients, there was no relationship between the severity of hypertension, assessed by the level of systolic and diastolic blood pressure, serum uric acid level and amount of proteinuria, and log (plasma) ANP levels. There was a significant negative correlation between serum sodium level and log (plasma) ANP level in all pregnant subjects (r=- 0.51, P < 0.05). Compared with non-pregnant women, plasma ANP levels are increased during the third trimester of normal pregnancy and in pregnancies complicated by pre-eclampsia. A relationship between ANP and pre-eclampsia seems unlikely but ANP is probably involved in the regulation of sodium and water balance in normal pregnancy and in pre-eclampsia.     

蛋白Z、蛋白Z依赖蛋白酶抑制剂及其他凝血指标与妊娠期高血压疾病的相关性分析

目的:研究蛋白Z(PZ)、蛋白Z依赖蛋白酶抑制剂(ZPI)及其他凝血指标[蛋白C(PC)、蛋白S(PS)]与妊娠期高血压疾病(HDP)的相关性。方法:收集2017年6月2018年12月在郑州大学第三附属医院产科收治的HDP患者60例作为研究对象(HDP组),其中妊娠期高血压组(25例)、子痫前期组(PE组,35例),另外选取健康孕妇50例作为正常妊娠组,未孕妇女30例作为正常未孕组。比较各组血清PZ、ZPI及血浆PS、PC水平,研究其与HDP的相关性,并采用受试者工作特征(ROC)曲线分析其对HDP的诊断价值。结果:①HDP组的血清PZ、ZPI水平均低于正常妊娠组(P<0.05),正常妊娠组高于正常未孕组(P<0.05),血清PZ、ZPI水平与HDP呈负相关(r分别为-0.687和-0.444,P<0.05),ROC曲线下面积分别为0.901(95%CI:0.853~0.948)、0.759(95%CI:0.676~0.841),最佳诊断截断值分别为31.52 ng/mL和14.54 ng/mL。②血浆PS、PC在HDP组低于正常妊娠组和正常未孕组(P<0.05),正常妊娠组与正常未孕组相比差异无统计学意义(P>0.05),血浆PC水平与HDP呈负相关(r为-0.304,P=0.000),PC对HDP诊断的最佳截断值为108.08%,AUC为0.677(95%CI:0.586~0.769)。血浆PS水平与HDP无相关性(P>0.05)。③HDP组2个亚组相比,PE组血清PZ、ZPI水平均低于妊娠期高血压组(P<0.05),而2组血浆PS、PC水平比较差异无统计学意义(P>0.05)。结论:检测妊娠期高血压疾病患者血清中PZ、ZPI及血浆中PS、PC水平,可以及早地发现凝血指标的异常,进行早期干预治疗,最大程度减少HDP的并发症。     

Urinary tissue kallikrein excretion in black African women with severe pre-eclampsia

BACKGROUND: A study of tissue kallikrein excretion in African women with severe pre-eclampsia. METHODS: Random untimed urine samples were collected from all women (n=198) recruited to this study; 66 women with severe pre-eclampsia, 66 normotensive pregnant women of similar length of gestation and 66 normotensive non-pregnant women. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (S2266) having the sequence H-D-Val-Leu-Arg-pNA. RESULTS: Urinary tissue kallikrein levels were decreased in women with severe pre-eclampsia compared with those of gestation matched normotensive pregnant women at 28 weeks of gestation (1.55+/-0.95 vs. 3.02+/-1.35 ng TK/microg protein; p<0.0001) and at near delivery date (1.21+/-0.53 vis. 3.11+/-1.2 ng TK/microg protein; p<0.0001). In the normotensive pregnant group, there was no significance difference in urinary tissue kallikrein excretion close at delivery date compared to 28 weeks of gestation (3.02+/-1.35 vs. 3.11+/-1.21 ngTK/microg protein; p=0.23). No statistical difference in urinary tissue kallikrein excretion was observed between normotensive pregnant and normotensive non pregnant women (3.02+/-1.35 vs. 2.97+/-1.12 ngTK/microg protein; p=0.16). Urinary tissue kallikrein excretion correlated positively with urinary creatinine levels at 28 weeks of gestation (r=0.69; p<0.0001) and close to delivery date (r=0.84; p<0.0001). There was no correlation between neonatal birthweight and urinary tissue kallikrein levels (r=-0.44; p=0.41). CONCLUSION: The decreased levels of urinary tissue kallikrein excretion in pre-eclamptic patients suggests an etiological role for this serine protease in hypertensive disorders of pregnancy.     

Serum levels of leukocyte functional antigen-3 in pregnancy and preeclampsia.

BACKGROUND: Adhesion molecules have been demonstrated to be involved in placental growth and development in normal pregnancy. Experimental evidence indicates that adhesion molecules are key factors of endothelial activation in preeclampsia. The aim of our study was to evaluate serum levels of the adhesion molecule Leukocyte Functional Antigen (LFA)-3 in healthy, non pregnant, female controls, healthy pregnant women, and preeclamptic women. METHODS: In our study we included 45 healthy, non pregnant, female controls, 45 healthy pregnant women, and 45 preeclamptic women. An enzyme-linked immunosorbent assay was used to determine serum levels of LFA-3. Results were correlated to clinical data. RESULTS: The median LFA-3 serum level in healthy, non pregnant, female controls was 0.2 (range 0 to 8.6) ng/mL. LFA-3 serum levels in healthy pregnant women were 4.8 (range 0 to 18) ng/mL and were significantly elevated compared to healthy, non pregnant, female controls (Mann-Whitney U-test, p=0.004). A cut-off level of 4.8 ng/mL was selected according to the 75th quantile of serum levels measured in the panel of healthy, non pregnant, female controls. In preeclamptic women, whose pregnancies had to be terminated due to exacerbation of preeclamptic symptoms, LFA-3 serum levels above the cut-off level were seen in 14/27 (52%) cases. In contrast, preeclamptic women, who went into spontaneous labor showed elevated LFA-3 serum levels in 17/18 (95%) cases (chi-square test, p=0.002). LFA-3 serum levels revealed a statistically significant influence on the odds of termination of pregnancy due to exacerbation of preeclamptic symptoms (unconditional logistic regression, p=0.02) with an odds ratio of 0.1 (95% CI, 0.006 to 0.7) by every doubling of LFA-3 values. CONCLUSIONS: Our results suggest that LFA-3 expression is upregulated in healthy pregnant women compared to healthy, non pregnant, female controls. Failure of LFA-3 upregulation in preeclampsia is associated with an increased risk for termination of pregnancy due to exacerbation of preeclamptic symptoms.     

Leptin and pre-eclampsia in black African parturients

Objective To measure serum concentrations of the hormone leptin during late pregnancy in Black African women with pre-eclampsia, healthy normotensive pregnant women as controls and healthy normotensive non-pregnant women; secondly, to explore the relationship between leptin and obesity.
Design Observational, cross sectional study.
Setting Antenatal clinics, antenatal wards, gynaecology out patient and family planning clinics of a tertiary hospital, Durban, South Africa.
Population Pregnant and non-pregnant Black African women.
Method Serum leptin was measured by a homologous radio-immunoassay technique. Simple anthropometric parameters were used to explore the relationship between leptin and obesity. In each group, leptin levels were compared between obese (body mass index,  BMI ≥ 30 kg m⁻²  ) and lean women.
Main outcome measures Serum leptin concentrations, anthropometric parameters, mean blood pressures and proteinuria.
Results There were 68 women with pre-eclampsia, 92 healthy normotensive pregnant women (controls) and 32 healthy normotensive non-pregnant women. Serum leptin levels were higher in pregnant compared with non-pregnant women [26.66 (1.96) and 25.89 (1.65) vs 17.97 (2.11) ng/mL,   P = 0.02  ]. Weight and BMI showed the greatest correlation with leptin both in pregnant (   r = 0.61 and r = 0.58, respectively  ) and non-pregnant women (   r = 0.74 and 0.79, respectively  ). There was no significant difference in the mean concentrations of leptin between women with and those without pre-eclampsia [26.66 (1.96) vs 25.89 (1.65) ng/mL, respectively,   P = 0.95  ].
Conclusion Pregnancy is a hyperleptinaemic state. There is no difference in serum leptin levels between Black African women with pre-eclampsia and healthy normotensive pregnant women. Serum leptin concentration is largely determined by the degree of adiposity.     

Lipid peroxidation in eclampsia.

In order to investigate the extent of lipid peroxidation in hypertensive disorders of pregnancy, a case-control study was designed. Eight eclamptic women were matched with women with severe pre-eclampsia (n = 8) and healthy pregnant controls (n = 8). Lipid peroxidation was measured by the malondialdehyde thiobarbituric acid reactive assay (MDA-TBAR) and expressed as nmol/ml. Both severe pre-eclampsia and eclampsia groups had significantly higher MDA-TBAR levels than healthy pregnant women. Eclamptic women before delivery had highest MDA-TBAR levels which decreased after delivery.     

Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia, but not normotensive intrauterine growth restriction

RATIONALE: Syncytiotrophoblast microparticles (STBM) are shed into the maternal circulation in higher amounts in pre-eclampsia compared to normal pregnancy and are believed to be the stimulus for the systemic inflammatory response and endothelial cell damage which characterises the maternal syndrome. The excess shedding of STBM may be caused by hypoxia as a result of poor placentation, which is often a feature of pre-eclampsia. Similar placental pathology occurs in some cases of normotensive intrauterine growth restriction (nIUGR), but in the absence of maternal disease. OBJECTIVE: To examine whether the shedding of STBM in nIUGR occurs to the same extent as in pre-eclampsia. METHODS: A prospective case-control study in a tertiary referral centre of: 1) women with early-onset pre-eclampsia (EOPET < 34 week), 2) women with late-onset pre-eclampsia (LOPET > or = 34 week), 3) women with nIUGR), 4) matched normal pregnant women (NPC), and 5) non-pregnant women. An ELISA using the antitrophoblast antibody NDOG2 was used to measure STBM levels in peripheral venous plasma. Non-parametric analyses were conducted with statistical significance set at p < 0.05. RESULTS: STBM levels rise during normal pregnancy. EOPET was associated with increased STBM levels (EOPET (median): 41 ng/ml, n = 15) compared with matched normal pregnancy (16 ng/ml, n = 15; Wilcoxon p = 0.005). LOPET (50 ng/ml, n = 10) and nIUGR (18 ng/ml, n = 8) STBM levels did not differ from matched normal pregnancy (36 ng/ml, n = 15, and 36 ng/ml, n = 8, respectively). Background levels in non-pregnant plasma were 0.49 ng/ml, n = 10. CONCLUSIONS: Increased STBM levels were found in EOPET but not in nIUGR providing further evidence for their role in the pathogenesis of the maternal syndrome.     

Prediction of pre-eclampsia with maternal mid-trimester total renin, inhibin A, AFP and free beta-hCG levels

We wanted to study if maternal serum mid-trimester total renin, inhibin A, AFP or free beta-hCG levels predict the development of pre-eclampsia. Maternal serum alpha-fetoprotein (AFP) and human chorion gonadotrophin (beta-hCG) were evaluated in the screening programme for Down syndrome in 4356 patients prospectively. Data on pregnancy outcome were available in 1242 women. Pregnancy-induced hypertension (PIH) developed in 69 women, 282 women with uneventful pregnancy outcome were selected for controls. Serum total renin and inhibin A levels were measured retrospectively in the trisomy screening samples of 69 and 30 patients who later developed PIH, and in 282 and 7 patients, respectively, who had an uneventful pregnancy outcome. No significant differences were found in the levels of maternal mid-trimester serum total renin, inhibin A or free beta-hCG levels between PIH and healthy women. The multiples of the median (MoM) of AFP values were significantly higher in the subgroup of patients who later developed severe pre-eclampsia than in patients with mild pre-eclampsia or gestational hypertension and healthy pregnant women. Maternal mid-trimester serum levels of total renin, inhibin A and free beta-hCG are not predictive for development of PIH. High mid-trimester serum AFP values may help in the prediction of severe pre-eclampsia.