Inhibin A levels and severity of preeclampsia

Objective  To evaluate the use of third trimester inhibin A levels to assess the severity of preeclampsia. Materials and methods  Blood samples were taken from women diagnosed with mild and severe preeclampsia during the third trimester of pregnancy. Blood samples were collected in plain tubes, centrifuged and stored at −80°C until analyzed. All serum samples were measured for inhibin A levels by enzyme-linked immunosorbent assays. Results  Inhibin A levels were greater in the severe (1,435.9 ± 603.2 pg/mL) than in the mild preeclampsia group (1,021.9 ± 438.8 pg/mL, P = 0.014). Conclusion  Inhibin A levels rise with increasing severity of disease. However, there is considerable overlap of serum inhibin A levels in women with mild and severe preeclampsia. Inhibin A is therefore not a useful adjunct for the classification of preeclampsia. This abstract was presented at the 15th Congress of the Federation of Asia and Oceania Perinatol Societies, Nagoya, Japan.     

Serum leptin concentrations throughout the menstrual cycle

Leptin is a cytokine involved in the regulation of food intake and fertility in rodents and in humans. No data exist about serum leptin serum levels during the spontaneous menstrual cycle. In this study 16 ovulatory cycles of endocrinologically normal volunteers were analyzed. Blood samples were taken on alternate days throughout the menstrual cycle for measurement of serum estradiol, progesterone, LH, FSH and leptin serum levels. No correlation of leptin values with estradiol values (r = 0.07) or progesterone values (r = 0.14) were seen. Mean leptin values during the luteal phase were significantly higher (16.67 ± 9.45 ng/mL) compared to the follicular phase (13.50 ± 8.75 ng/mL) (P < 0.02). A strongly positive correlation with the progression of the menstrual cycle could be seen (r = 0.91). The physiological significance of higher luteal phase leptin levels is unknown. Received: December 1998 / Accepted: 25 May 1999     

瘦素在子癎前期患者胎盘和血清的表达和意义

目的 探讨子癎前期患者胎盘和血清中瘦素的表达变化及其和子癎前期发病的关系.方法 采用免疫组化SP法检测45例子癎前期患者(研究组,其中重度组28例,轻度组17例)和30例同期正常妊娠妇女(对照组)胎盘瘦素水平,并用酶联免疫吸附实验检测两组孕妇产前血清瘦素水平.结果 (1)两组胎盘瘦素均在合体滋养细胞胞浆表达,随病情加重,染色逐渐加深,胎盘瘦素与子癎前期存在线性相关关系.(2)研究组、轻度组、重度组和对照组血清瘦素浓度分别为(10.41±4.78)ng/ml、(6.33±1.87)ng/ml、(12.88±4.27)ng/ml、(5.73±2.19)ng/ml,轻度组稍高于对照组但无统计学意义(P>0.05),研究组和对照组、轻和重度组、重度组和对照组相比,均有性统计学意义(P<0.01),瘦素表达水平和病情严重程度呈正相关.(3)血清瘦素与体重指数无相关性(P>0.05);但其与收缩压、舒张压及平均动脉压均呈正相关(r=0.602、0.566和0.585,P均<0.05).结论 瘦素在子癎前期患者胎盘和血清中均高表达,高瘦素水平参与子癎前期的发生和发展.     

Placental leptin in HIV-associated preeclampsia

Objective

HIV-associated preeclampsia reflects a combination of opposing influences on the immune status. The adipocyte hormone leptin has been implicated in the pathophysiology of preeclampsia and in enhancing immunity. This study is the first, to our knowledge, to determine whether leptin levels in the placenta differ between HIV-associated normotensive and preeclamptic pregnancies. The study also compares leptin levels between the exchange and conducting areas of the placenta.

Study design

Pregnant women were recruited antenatally and grouped as follows: normotensive HIV uninfected (n = 30), normotensive HIV infected (n = 60), preeclamptic HIV uninfected (n = 30) and preeclamptic HIV infected (n = 60). Anthropometric data were collected and placental leptin was analysed by immunohistochemistry and ELISA.

Results

Leptin levels were similar in the central and peripheral regions of the placenta. Leptin immunoreactivity was observed amongst the different trophoblast cell populations. Both ELISA and immunohistochemistry of the placental exchange villi indicated that leptin levels were higher in preeclampsia compared to normotensive pregnancies (p < 0.001). HIV status had no effect on leptin levels but levels were higher in participants on highly active antiretroviral treatment (HAART) compared to those on prophylaxis for prevention of mother to child transmission (PMTCT) with normotensive (p = 0.006) and preeclamptic (p = 0.002) pregnancies. The area of immunostaining was greater in the exchange compared to the conducting villi in HIV infected and uninfected preeclampsia.

Conclusions

This novel study establishes an elevation of leptin in preeclamptic placentae, irrespective of HIV status. Leptin elevation was not focal in that it occurred in both central and peripheral regions of the preeclamptic placenta. This suggests a role of leptin in the pathophysiology of preeclampsia.     

Serum leptin levels in hypertensive disorder of pregnancy

OBJECTIVE: To determine serum leptin levels in hypertensive disorder of pregnancy. MATERIALS AND METHODS: In this prospective, cross-sectional, case control study, we measured serum leptin levels of 58 hypertensive pregnant women and 54 normal pregnant women. We also did blood and urine analysis for the evaluation of the severity of hypertensive disorder of pregnancy. The patients were followed until after delivery and information about labour was recorded. We analysed the difference and correlation between anthropometric measures, hormonal and biochemical parameters, and serum leptin levels in two groups. RESULTS: In the study group, serum leptin levels were determined to be higher than the control group. Neonatal birth weight was significantly lower in the hypertensive group. While the serum uric acid, urea, aspartate aminotransferase, fibronectin, and fasting blood glucose levels were found to be higher, serum total protein and albumin levels were significantly lower among the hypertensive pregnant women. Hypertensive pregnant women were more insulin resistant. Serum leptin levels were highly and positively correlated with serum fibronectin, and C peptide levels. A negative significant correlation was observed between maternal serum leptin levels and neonatal birth weight among the pregnant women having the hypertensive disorders. CONCLUSION: Serum leptin levels in hypertensive pregnant women appear to be higher. The determination of serum leptin levels may be as important as serum fibronectin and C peptide levels in the management of hypertensive disorder of pregnancy. C peptide and insulin may be due to hyperinsulinemia which leads to increased stimulation of leptin production by fatty tissue. Insulin resistance which appears in late pregnancy is more significant especially in pregnancies complicated by preeclampsia.     

Multicentric reticulohistiocytosis in a patient with severe preeclampsia

A multigravida patient with polyarthralgia and eruptions on the head and fingers was seen at 6 weeks’ gestation. No histological examination was performed before the current pregnancy. She developed severe early onset preeclampsia associated with swelling of the knees and increased cutaneous nodules, biopsies of which revealed multicentric reticulohistiocytosis. At 28 weeks’ gestation an elective cesarean section was performed and a 580-g male infant was delivered. Received: June 1999 / Accepted: 23 September 1999     

脂源性细胞因子与子痫前期关系的研究

目的:探讨子痫前期(PE)患者血清脂源性细胞因子(脂联素和瘦素)水平的变化及其意义。方法:以53例子痫前期孕妇为研究组(其中轻度子痫前期32例、重度子痫前期21例),20例同期分娩的正常孕妇为对照组。采用ELISA法检测血清脂联素和瘦素水平。同时检测血清甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平。结果:(1)轻度、重度子痫前期患者血清脂联素水平分别为8.88±4.67μg/m l及5.14±2.79μg/m l,明显低于对照组11.61±2.90μg/m l,差异有统计学意义(P<0.01)。而轻度、重度子痫前期患者血清瘦素水平为21.79±15.19ng/m l及27.27±18.38ng/m l,明显高于对照组的12.35±6.51ng/m l,差异有统计学意义(P<0.05,P<0.01),(2)子痫前期患者血清脂联素与TG、TC、LDL-C、HDL-C均显著相关(r分别为-0.658、-0.624、-0.419、0.461),瘦素水平也与上述指标显著相关(r分别为0.534、0.707、0.418、-0.513),(3)子痫前期患者血清脂联素及瘦素水平呈高度负相关(r=-0.760,P<0.01)。结论:脂联素、瘦素等脂源性细胞因子在PE的发病中可能起一定的作用。     

Altered mRNA expression of ecNOS and iNOS in myometrium and placenta from women with preeclampsia

Objective: Preeclampsia is a syndrome involving dysfunction of vascular endothelium and imbalance between endothelium derived constricting and relaxing factors. Recent evidence suggests that endothelium-derived nitric oxide (NO) plays a role in the regulation of vascular resistance during normal pregnancy and preeclampsia. NO is a potent vasodilator and is generated by the catalytic action of nitric oxide synthases ecNOS and iNOS in myometrium and placenta. Methods: In this study mRNA expressions of ecNOS and iNOS were compared in myometrium and placenta. Biopsies were collected from women with preeclampsia (n=8) and normal pregnancies (n=12). ecNOS and iNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction for control GAPDH gene mRNA levels. Results: The mRNA expression of ecNOS was significantly higher in both myometrium (p<0.05) and placenta (p<0.05) from women with preeclampsia compared to that in normal pregnancies, while the iNOS mRNA level was not altered in myometrium and lower in placenta (p<0.05) from women with preeclampsia. Conclusions: The higher ecNOS mRNA expression might be a compensatory response to an impaired vasodilatation in the uteroplacental circulation during preeclampsia. Whether the similar and reduced levels of iNOS mRNA expression in myometrium and placenta, respectively, in women with preeclampsia is of importance remains to be further evaluated. Received: 30 October 2000 / Accepted: 30 October 2000     

Maternal levels of vitamin E in normal and preeclamptic pregnancy

Vitamin E, a potent antioxidant, may play a role in preventing preeclampsia. Maternal blood samples were collected between 28 and 40 weeks’ gestation from women with mild preeclampsia (n=17), women with severe preeclampsia (n=16) and the control group (n=15). This control group was consisted of 15 pregnant women without hypertension episode during their pregnancy. Vitamin E levels were significantly higher in normotensive pregnant women (1.00±0.20 mg/dL) than in those with mild (0.56±0.15 mg/dL) or severe (0.37±0.75 mg/dL) preeclampsia (P<0.001). In preeclamptic women, when systolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05), also when diastolic blood pressure increases, maternal levels of vitamin E significantly decrease (P<0.05). Measurement of vitamin E concentration in plasma may be useful as a prognostic marker of the likely development of preeclampsia. Received: May 1999 / Accepted: 7 December 1999     

Endostatin levels and the risk of subsequent preeclampsia

Objective

To evaluate endostatin, an anti-angiogenic factor, in relation to the risk of preeclampsia (PE).

Study design

In this case control study, serum samples were collected at 11–17 weeks and 18–26 weeks’ gestation. Endostatin levels were expressed as adjusted multiples of the median (MoM). Logistic regression was used to calculate adjusted odds ratios (aORs) for the prediction of PE.

Results

A total of 77 women with PE and 150 controls were studied. Endostatin levels were significantly higher in women with PE compared to controls in both the first and the second trimester. At a cut-off level of 75th percentile of endostatin MoMs, the aORs for PE were 1.33 (95% confidence interval [CI], 0.68–2.58) at 11–17 weeks and 1.77 (95% CI, 0.94–3.34) at 18–26 weeks, after adjustment for ethnicity and chronic hypertension. The aORs for early-onset PE were 3.51 (95% CI, 1.18–10.43) at 11–17 weeks and 2.17 (95% CI, 0.67–7.06) at 18–26 weeks.

Conclusions

Higher endostatin levels are associated with an increased risk of early onset PE. Endostatin alone, however, has a poor predictive value for clinical usefulness.     

Correlations between circulating levels of adipokines and anti-angiogenic factors in women with BMI <30 and a late-onset preeclampsia

Preeclampsia (PE) is a pregnancy-specific disease, directly related to high rates of maternal–fetal morbidity and mortality worldwide. Upregulation of anti-angiogenic factors (soluble fms-like tyrosine kinase-1; sFLT-1 and soluble endoglin; sENG) have been suggested to trigger the maternal endothelial dysfunction observed in PE. Studies focusing on the role of adiponectin and leptin, in normal pregnancy as well as in complicated pregnancies, have revelated interesting findings due to the vascular actions of such adipokines. The aims of this study were to compare plasma concentrations of the adiponectin, leptin, sENG and sFLT-1 in preeclamptic (PE, n?=?27) and healthy pregnant (HP, n?=?36) and to evaluate possible correlations among these adipokines and anti-angiogenic factors. There were significant increases in all biomarkers in PE compared to HP (all p?r?=?0.85 and r?=?0.47, respectively) and sEng (r?=?0.74 and r?=?0.56, respectively). Moreover, we observed significantly correlation among body mass index (BMI) with adiponectin (r?=??0.40) and with leptin (r?=?0.51) in HP, but not in PE. Moreover, while a negative correlation between sFLT-1 and BMI (r?=??0.60) was found in PE, no correlation was observed regarding sEng and BMI. In summary, our findings suggest the existence of a compensatory mechanism that occurs in an attempt to correct this angiogenic imbalance in order to restore the fetal development.     

The effect of methyldopa treatment on uterine,umblical and fetal middle cerebral artery blood flows in preeclamptic patients

The purpose of this study was to evaluate the efficacy of methyldopa in the treatment of preeclamptic patients. This study was performed on 24 preeclamptic women who were in between 25–36 weeks of gestational age. 24 healthy pregnant women were taken as control group. Before starting treatment, 24 preeclamptic patients were examined with Doppler ultrasound. Pulsatility index, resistance index, systolic/diastolic ratio of uterine, umblical and fetal middle cerebral arteries were measured. Preeclamptic patients were treated with totally 1 g methyldopa per day. After 7 d, patients were reexamined with Doppler ultrasound. The effect of methyldopa on uterine, umblical and fetal middle cerebral artery blood flows were detected. Only one control with Doppler ultrasound was done to the healthy pregnant women. Before methyldopa treatment to the preeclamptic women, pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D) on uterine and umblical arteries were significantly higher than the control group. However, fetal middle cerebral artery (MCA) values were significantly lower than the control group. When Doppler results of preeclamptic patients before and after the methyldopa treatment were compared, no significant differences in terms of Pulsatility Index, Resistance IndexI and S/D ratio of umblical and fetal middle cerebral arteries were found. However, the results of uterine artery were significantly lower after the treatment in preeclamptic patients. Treatment with methyldopa lowered the uterine artery resistance in preeclamptic patients but did not effect the resistance of umblical and fetal middle cerebral artery. Received: 27 March 2001 / Accepted: 5 June 2001     

The association between preeclampsia and the severity of gestational diabetes: the impact of glycemic control

OBJECTIVES: We sought to determine if the rate of preeclampsia is related to the severity of gestational diabetes mellitus (GDM), and if it can be decreased by optimizing glycemic control. STUDY DESIGN: A retrospective analysis of prospectively collective data of 1813 patients with GDM was performed to determine the rate of preeclampsia. Patients were stratified after treatment was begun by level of glycemic control (well controlled was defined as mean blood glucose <95 mg/dL). The extent of hyperglycemia was analyzed by the level of the abnormality in the oral GTT and by the degree of abnormality of daily glucose control after treatment has begun. Severity of GDM was categorized using fasting plasma glucose (FPG) on a 3-hour oral GTT by 10 mg/dL increments. RESULTS: Overall, preeclampsia was diagnosed in 9.6% (174/1813) of diabetic patients. The GDM subjects who developed preeclampsia were significantly younger, had a higher nulliparity rate, were more obese, and gained significantly more weight during pregnancy. However, no difference was found in glycemic profile characteristics between the 2 groups. A comparison between patients with FPG <105 and FPG >105 revealed that the rate of preeclampsia increased significantly, 7.8% vs 13.8%, (O.R 1.81, 95%CI 1.3-2.51). For GDM patients with only mild hyperglycemia (FPG <105 mg/dL), no significant difference was found in the rate of preeclampsia. Preeclampsia rate was further evaluated in relation to level of glycemic control; for the well-controlled patients (mean blood glucose [MBG] <95 mg/dL, n=994), similar rates of preeclampsia were found between each category of FPG severity. In contrast, in poorly controlled patients (MBG >95 mg/dL, n=819), a comparison between severity threshold of FPG <115 and FPG >115 revealed that the preeclampsia rate was 9.8% vs 18% (O.R 2.56, 95%C.I. 1.5-4.3). In a logistic regression model, only prepregnancy BMI (O.R 2.3, 95%CI 1.16-2.30) and severity of GDM (O.R 1.7, 95%CI 1.21-2.38) were independently and significantly associated with an increased risk of preeclampsia. CONCLUSION: The rate of preeclampsia is influenced by the severity of GDM and prepregnancy BMI. Optimizing glucose control during pregnancy may decrease the rate of preeclampsia, even in those with a greater severity of GDM.     

Increased expression levels of E-cadherin,cytokeratin 18 and 19 observed in preeclampsia were not correlated with disease severity

Introduction

Preeclampsia is a pregnancy-specific disorder and placental factor(s) contribute to the pathogenesis of preeclampsia. Turnover of villous trophoblast is affected by impaired placental perfusion in preeclampsia. Expression and localisation of cadherins and cytokeratins are involved in the pathogenesis of preeclampsia. However, studies describing the associations between cadherins and cytokeratins in preeclampsia are limited. The aim of this study was to investigate the expression of E-cadherin, N-cadherin, cytokeratin 18 and cytokeratin 19 in placentae from women with preeclampsia in order to determine whether their expression differs with disease severity.

Methods

29 preeclamptic placentae and 25 normotensive placentae were included in this study. The expression of E-cadherin, cytokeratin 18, cytokeratin 19 andN-cadherin was quantified by immunohistochemistry and western blotting.

Results

E-cadherin, cytokeratin 18 and cytokeratin 19 were expressed predominantly in the syncytiotrophoblast of the placenta and the expression of E-cadherin, cytokeratin 18 and cytokeratin 19 was significantly increased in preeclampsia compared to normotensive pregnancies. However, there was no significant difference in expression between severe preeclampsia and mild preeclampsia. In addition, there was no difference in the expression of N-cadherin between preeclampsic and normotensive pregnancies.

Discussion

Our data demonstrated increased expression of E-cadherin, cytokeratin 18 and cytokeratin 19 in the syncytiotrophoblast of preeclamptic placentae, but this increase was not correlated with disease severity.

Conclusion

Our data suggests that E-cadherin and cytokeratins are involved in the pathogenesis of preeclampsia.     

血清、脐血中MPO水平变化及胎盘组织MPO mRNA表达与子痫前期发病的关系

目的:研究重度子痫前期(PE)患者血清MPO及胎盘组织中MPO mRNA表达水平变化与PE发病的关系,探讨糖脂代谢异常及氧化应激在PE病理生理机制中的可能作用。方法:选取60例重度PE孕妇,按发病时孕周不同分为早发型PE组(孕周34周)和晚发型PE组(孕周≥34周)各30例。另选取同期健康晚期妊娠孕妇60例,分为对照1组(孕周34周)和对照2组(孕周≥34周)各30例。采用实时荧光定量PCR技术检测胎盘组织中MPO mRNA表达水平;ELISA法检测血清MPO水平。检测患者血压、血脂、血糖、胰岛素水平等指标,进行相关性分析。结果:PE组的血清MPO水平高于对照组(P0.05),且早发型高于晚发型PE组(P0.05);但对照组间比较无差异(P0.05)。PE组的血清TC、TG、LDL、FINS、HOMA-IR分别高于对照组(P0.05),HDL水平低于对照组(P0.05);但PE组间比较及对照组间比较,均无差异(P0.05)。PE组的脐血MPO水平、胎盘组织中MPO mRNA表达水平均高于对照2组(P0.05),且早发型高于晚发型组(P0.05)。PE组的血清MPO水平与TG、HoMA-IR、FINS、胎盘组织MPO mRNA表达水平均呈正相关(r=0.557、0.615;0.694、0.511;0.766、0.717;0.696、0.695),与血HDL呈负相关(r=-0.697,-0.576);对照2组则无相关性。结论:MPO可能参与了PE的病理生理过程。胎盘组织中MPO mRNA表达水平升高可能是血清MPO水平升高的重要原因。PE患者血脂代谢异常及胰岛素抵抗增加与血清MPO水平升高有关,它们可能参与了血清MPO水平升高后促发PE的氧化应激的病理生理过程。     

Association between serum CA125 levels in preeclampsia and its severity among women in Lagos,South-West Nigeria

Background: Preeclampsia is a syndrome of unknown etiology characterized by hypertension, proteinuria, and/or organ dysfunction. CA125 is an antigenic determinant recognized by the murine monoclonal antibody OC125 quantified by radioimmunoassay. Its role in obstetrics is yet to be fully understood as most clinical trials advocating its uses are widely experimental in nature and unacknowledged. Aim: This study was done to assess the relationship between serum concentration of CA125 in normal pregnancies and those complicated with preeclampsia. Methods: A case–control study involving 70 women diagnosed with preeclampsia and 70 healthy controls matched for age, parity, and gestational age at enrollment. Venous samples were collected from each participant after informed consent was obtained. The preeclampsia group was further subdivided into mild and severe preeclampsia and all participants were followed up till delivery with records of delivery, maternal, and neonatal outcomes obtained thereafter. Serum CA125 levels were determined by standard enzyme-linked immunosorbent assay (ELISA) method. Hypothesis testing was done using chi-square test for categorical variables, and the independent-samples t-test and ANOVA for numerical variables. All significances were reported at P < 0.05. Results: The mean serum level of CA125 in women with preeclampsia was significantly greater than those with normal pregnancy (54.17 IU/mL vs. 12.49 IU/mL, P < 0.05). CA125 level also correlated positively with systolic blood pressure (r = 0.406, P < 0.05), diastolic blood pressure (r = 0.433, P < 0.05), serum uric acid levels (r = 0.407, P = 0.001), platelet levels (r = 0.341, P = 0.001), and urinary protein levels (r = 0.325, P = 0.002). The CA125 levels between the three categories of participants in the study were: normotensive control (12.49 ± 6.62 mIU/L), mild preeclampsia (29.43 ± 3.7 mIU/L), and severe preeclampsia (64.25 ± 9.21 mIU/L), respectively (P = 0.023). Conclusion: We can infer from this study that increased maternal serum CA 125 levels are associated with the preeclampsia and its severity. However, further validation of these findings with more robust multicenter prospective and longitudinal characterization of maternal serum CA125 profiles in pregnancy should be carried out in subsequent investigations to determine its suitability as a predictive biomarker for preeclampsia in women of African descent.     

Distribution of ABO and Rh blood groups in patients with HELLP syndrome

The aim of this retrospective study was to evaluate the relationship between HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and the maternal blood groups. Five hundred and forty-seven women with severe preeclampsia were included and divided into eight groups according to their blood groups: A Rh-positive (n=203), A Rh-negative (n=38), B Rh-positive (n=83), B Rh-negative (n=10), 0 Rh-positive (n=148), 0 Rh-negative (n=21), AB Rh-positive (n=39), and AB Rh-negative (n=5). The groups were controlled by analysis of variance and found to be homogenous with respect to parity, gestational age, blood pressure, hemoglobin, hematocrit, platelet values, prothrombin time, partial thromboplastin time, fibrinogen, creatinine, alanine aminotransferase, aspartate aminotransferase, bilirubin, uric acid, and proteinuria. Incidence of HELLP syndrome was 24% in the overall study population whereas 48% of the patients with the blood group O Rh-negative had HELLP syndrome associated with an increase in risk by a factor of 3.1. To our knowledge this is the first report of such an association. Received: 13 August 2001 / Accepted: 25 September 2001 Correspondence to M. Sezik