Activated protein C resistance in Turkish women with severe preeclampsia

The purpose of this study was to investigate the occurrence rate of APC resistance (APC-R) with severe preeclampsia in Turkish women. Thirty-two consecutive women having severe preeclampsia were included in the study. Thirty-two healthy pregnant women served as the control group. APC-R assays were performed in the third trimester of pregnancy, and 3 and 9 months after delivery. APC-R was demonstrated in the third trimester, 3 months and 9 months after delivery in 27 (84.4%), 23 (71.9%) and 5 (15.6%) of 32 preeclamptic patients, respectively. APC-R rates were significantly higher in preeclamptic group than in normal pregnant women in the third trimester of pregnancy (p < 0.05). Decreased mean APC activity and also increased APC-R rate was still persisting in preeclamptic group for 3 months after delivery. Nine months after delivery, the mean APC activity and also APC-R rates approached to the normal pregnant women; however, there was a significant difference between both groups (p < 0.05). Our results indicate that acquired APC-R may be a contributory factor in the pathogenesis of preeclampsia.     

Ultrastructural aspects of preeclampsia. II. Mitochondrial changes

Biopsy specimens were obtained under direct vision at the time of cesarean section from 47 patients (35 with preeclampsia and 12 normotensive patients) and from four women with cesarean section hysterectomies (all normotensive) as an extension of previous work. Tissues were obtained from the myometrium near the placental bed and from the opposite side of the uterus. Skin biopsies were also obtained from eight women with preeclampsia and liver biopsies were obtained from two patients with acute microvesicular fatty change of pregnancy (one with and one without concomitant preeclampsia). Specimens were examined histologically and by electron microscopy. Mitochondrial changes in small vessels, principally venules, in myometrial smooth muscle, myometrial interstitial cells, circulating leukocytes, epidermal and dermal cells, and hepatocytes were examined and compared between women with preeclamptic and normotensive pregnancies. These findings were then compared with mitochondria from 500 biopsies over the same 3-year interval to assess the possible role of delay in tissue fixation. There were 12 other biopsies from nonpregnant women of childbearing age. As further control on artifact, other specimens were initially sampled immediately in the operating room and then serially for up to 2 hours later. Artifact as a basis for the mitochondrial changes was ruled out by these procedures. Normal mitochondria undergo a morphologic conformational sequence with physiologic changes in substrate, oxygen consumption, adenosine diphosphate, and respiratory rate. The mitochondria of preeclamptic tissues show a central disruption that is outside this normal sequence or cycle. This disruption occurs more often and is more severe in preeclampsia than in normotensive pregnancies. In addition, the hypertrophic smooth muscle of the pregnant uterus has a complex of cytoplasmic organelles in a paranuclear location, usually apical, that contains a variable mixture of glycogen, the Golgi apparatus, endoplasmic reticulum, mitochondria, and small unidentified microvesicles. This complex has the location and appearance suggestive of a myometrial "power pack" of significance in metabolism and contraction. The presence of similar mitochondrial changes in a limited sample of nonuterine tissues is suggestive of a systemic metabolic disorder as an important feature of preeclampsia.     

血清中脂联素水平变化及脂肪组织中脂联素mRNA表达与子痫前期发病的关系

-0.446(P均<0.05);对照组孕妇大网膜脂肪组织中脂联素mRNA表达水平与孕前体重指数呈明显负相关(r=-0.436,P<0.05).结论 子痈前期孕妇血清脂联素水平降低,提示其可能参与了子痫前期的病理生理过程;而子痫前期孕妇大网膜脂肪组织中脂联素mRNA表达水平显著下降,可能是子痫前期孕妇血清脂联素水平下降的主要原因.     

血清中脂联素水平变化及脂肪组织中脂联素mRNA表达与子痫前期发病的关系

-0.446(P均<0.05);对照组孕妇大网膜脂肪组织中脂联素mRNA表达水平与孕前体重指数呈明显负相关(r=-0.436,P<0.05).结论 子痈前期孕妇血清脂联素水平降低,提示其可能参与了子痫前期的病理生理过程;而子痫前期孕妇大网膜脂肪组织中脂联素mRNA表达水平显著下降,可能是子痫前期孕妇血清脂联素水平下降的主要原因.     

Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas

OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at <37 and <35 weeks of gestation, small-for-gestational-age infant, abruptio placentae, and perinatal death. Data were compared by using chi-square analysis and Wilcoxon rank sum test. RESULTS: The rates of preeclampsia and of severe preeclampsia were significantly higher in the previous preeclamptic group as compared to the nulliparous group (17.9% vs 5.3%, P <.0001, and 7.5% vs. 2.4%, P <.0001, respectively). Women who had recurrent preeclampsia experienced more preterm deliveries before 37 and 35 weeks of gestation than nulliparous women who developed preeclampsia. In addition, among women who developed severe preeclampsia, those with recurrent preeclampsia had higher rates of preterm delivery both before 37 weeks (67% vs 33%, P =.0004) and before 35 weeks of gestation (36% vs 19%, P =.041), and higher rates of abruptio placentae (6.7% vs 1.5%) and fetal death (6.7% vs 1.4%) than did nulliparous women. CONCLUSION: Compared to nulliparous women, women with preeclampsia in a previous pregnancy had significantly higher rates of preeclampsia and adverse perinatal outcomes associated with preterm delivery as a result of preeclampsia.     

Hypocalciuria in women with preeclampsia]

To assess the significance of hypocalciuria in pregnant women, 24-hour urinary calcium excretion and the calcium/creatinine ratio (mg/g) in random urine samples were measured with a Toshiba TDA-30R autoanalyzer in the following 4 groups: 3 mild preeclamptic patients, 5 severe preeclamptic patients, 4 patients with intrauterine growth retardation (IUGR), and 10 healthy pregnant women. The mean 24-hour urinary calcium excretion in the 4 groups was 44.3 +/- 21.3 mg/day, 11.6 +/- 2.7 mg/day, 161.4 +/- 80.4 mg/day and 145.0 +/- 45.0 mg/day, respectively. Calcium excretion was significantly lower in the mild and severe preeclamptic patients than in the women with IUGR and the normal pregnant women. There was also a significant difference between the value in the mild and severe preeclamptic patients. The mean calcium/creatinine ratio in random urine samples was 53 +/- 30 mg/g, 18 +/- 5.6 mg/g, 192 +/- 85 mg/g and 169 +/- 70 mg/g, respectively. Also, such significant as 24-hour urinary calcium excretion were found in the mean calcium/creatinine ratio. From these results we conclude that determination of the 24-hour urinary calcium excretion or the calcium/creatinine ratio in random urine samples is a reliable index of preeclampsia.     

Prediction of superimposed preeclampsia using uterine artery Doppler velocimetry in women with chronic hypertension

OBJECTIVE: To assess the role of uterine artery (UtA) Doppler to predict superimposed preeclampsia in women with chronic hypertension. METHODS: In a cohort of 182 women with chronic hypertension, UtA Doppler studies were performed before 25 weeks (mean 19.7 +/- 2.1 weeks) and repeated later in pregnancy (mean 28.5 +/- 3.7 weeks). RESULTS: The incidence of preeclampsia was 13% (24/182). Rates of preeclampsia increased with advancing gestation of abnormal UtA Doppler: 7% when UtA Doppler were normal at early exam, 18% when abnormal at early exam, and 28% when abnormal at late exam (Chi-square for trend: P < 0.001). The rate of preeclampsia among 40 women with abnormal early but normal late UtA Doppler was similar to that of women with normal findings at early exam (8 vs 7%; P = 1.00). Logistic regression analysis showed that the ability of UtA Doppler to predict preeclampsia was independent from other variables [Odds Ratio (OR) 7.1, 95% Confidence Interval (CI) 2.6-18.9). Receiver operating characteristic (ROC) curve identified a UtA value of 0.58 as the optimal threshold for the prediction of preeclampsia. CONCLUSION: The later in pregnancy the abnormal UtA Doppler findings are observed, the greater the risk of preeclampsia. Normalization of UtA Doppler after 25 weeks reduces the risk of preeclampsia to 8%.     

No difference in structure between omental small arteries isolated from women with preeclampsia,intrauterine growth restriction,and normal pregnancies

OBJECTIVE: Our purpose was to investigate whether there were structural differences between omental small arteries isolated from women with preeclampsia and intrauterine growth restriction and those isolated from women with normal pregnancy. STUDY DESIGN: A pressure myograph was used to study omental small arteries isolated from women with normal pregnancy and women with preeclampsia and intrauterine growth restriction (n = 16, 13, and 8, respectively). With the use of a transilluminating system, lumen diameter, wall thickness, wall/lumen ratio, distensibility, and the stress-strain relationship were studied through pressure ranges of 5 to 100 mm Hg. Arteries were then fixed with glutaraldehyde at the predelivery mean arterial pressure and embedded in epoxy resin. One-micrometer transverse sections were cut for more detailed morphologic examination. RESULTS: Wall thickness, lumen diameter, wall/lumen ratio, distensibility, and the stress-strain relationship of omental small arteries did not differ between patient groups (P >.05; repeated-measures analysis of variance). Detailed histologic examination confirmed these findings. CONCLUSIONS: Alterations in systemic vascular resistance associated with compromised pregnancies are unlikely to result from or produce an alteration in the structure of omental small arteries.     

Risk of coronary artery disease in women with history of pregnancies complicated by preeclampsia and LBW

Women with a history of pregnancy complicated by preeclampsia or intrauterine growth restriction and low infant birth weight looks at a higher risk for subsequent ischemic heart disease. Objective: To determine the relationship between pregnancy complications and maternal coronary artery disease (CAD) in the future. Materials and method: We performed a case-control study on 690 patients (345 patients in each group) referred to Tehran Heart Center. Women with CAD were in the case group and women without CAD were in the control group. The history of pregnancy complications (including preeclampsia, low birth weight [LBW] delivery, preterm labor and gestational hypertension) was evaluated in the two groups. Results: 12.5% of the patients in the case group had a history of preeclampsia, compared with the control group (1.7%). (p?<?0. 0001). Seven percent of the patients in the case group and 0.9% of the patients in the control group had history of LBW delivery. The difference was significant (p?<?0.0001). A history of preterm labor was recorded in 11% of cases and 3.2% of controls. Performing multivariate analysis showed that there is a strong association between preeclampsia and CAD (OR: 16.92; 95% CI; p?<?0.0001), LBW delivery and CAD (OR: 6.52; 95% CI; p: 0.0038), and also between high parity and CAD. (OR: 1.135; 95% CI; p: 0.0479). Conclusion: Our results suggest preeclampsia, LBW delivery and high parity of the mother as independent risk factors for CAD in the future.     

Insulin resistance in preeclampsia

Contemporary scientific data show that there is a link between insulin resistance and preeclampsia. Many features of the insulin resistance syndrome are common with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity and lipid abnormalities. The women with preeclampsia are more insulin resistant than those with normal pregnancy. The surrogate markers of insulin resistance like leptin, TNF-alpha, tissue plasminogen activator, SHBG etc are also changed in preeclampsia. Whether these changes are connected with etiology or with the pathogenesis of preeclampsia is still not clear.     

早发型重度子(癎)前期母体子宫动脉及胎儿血流动力学的研究

目的通过观察分析早发型重度子痢前期母儿血液动力学变化特点，结合其母儿预后，进一步探讨母儿血流动力学监测在早发型重度子痢前期的临床诊治及预后估计中的应用价值。方法采用前瞻性病例一对照研究方法，应用彩色多普勒超声对36例早发型重度子痢前期和72例正常同期孕妇进行血液动力学有关参数测定（包括UA-S／D、UA—PI、MCA—S／D、MCA-PI、UtA—S／D、UtA-PI），并结合其预后进行统计分析。结果在早发型重度子痢前期组和正常妊娠组，胎儿UA、MCA血流及孕妇UtA血流的S／D、PI值均随着妊娠的进展，呈逐渐下降的趋势，早发型重度子痢前期的UA—S／D，UA-PI，UtA-S／D，UtA-PI比正常妊娠时明显增高（P〈0．05），而MCA-S／D和MCA—PI在妊娠33周前则比正常妊娠组降低，妊娠33周后有显著性差异。当早发型重度子痢前期出现母胎血流动学变化时，围产儿不良结局的发生率高于正常妊娠组。本研究中有7例胎儿产前出现脐动脉舒张末期血流缺如（AEDV），全部合并FGR，围产儿死亡6例。结论母胎血流动学参数在早发型重度子痢前期时常发生明显的改变，并与不良的围产儿结局有关，AEDV的出现意味着胎儿循环已出现或临近失代偿阶段，警示预后不良。     

Serum homocysteine levels in pregnant women with preeclampsia

Preeclampsia is one of the most common and severe pregnancy complications, which ethiology remains unclear. It is certain that endothelial dysfunction plays a key role in the development of preeclampsia. Homocysteine is an important independent cardiovascular risk factor, which might induce the endothelial dysfunction observed in preeclampsia. 26 pregnant women--14 with preeclampsia (group 1) and 12 healthy term pregnant controls (group 2) were enrolled in the study between December 2003 and August 2004. Six of the women in this group had a superimposed preeclampsia. The mean homocysteine level in the first group was 11,04 mol/l, while in the control group it was 6,24 micromol/l (p < 0.05). The women with a severe preeclampsia had a significantly higher serum homocysteine levels than those with mild form (F = 0.025). Seven of the patients (50%) gave birth before 34th weeks of gestation. The study finds a link between the serum homocysteine as an endothelial dysfunction marker and the development of preeclampsia and a relation between the severity of preeclampsia and the degree of the elevation of the serum homocysteine levels.     

Cervicovaginal fetal fibronectin levels in women with preeclampsia

OBJECTIVE: To estimate the mean levels of fetal fibronectin in cervicovaginal secretions of women with preeclampsia and compare them with levels in normotensive controls. METHODS: Cervicovaginal swabs were obtained before digital examination from women who presented to labor and delivery for evaluation of preeclampsia and compared with fetal fibronectin levels from a group of control subjects with a similar gestational age. Fetal fibronectin was assayed by a specific enzyme-linked immunoassay. A concentration greater than 50 ng/mL was considered a positive result. RESULTS: Forty women with preeclampsia (17 mild and 23 severe) and 31 normotensive women were analyzed. The control group had 9.7% positive fetal fibronectins, whereas the preeclampsia group had 15% positive, P =.72, with 80% power to detect a 22% difference. The majority of the quantitative values in both groups were less than 20 ng/mL. There was not a significant difference between the two groups in quantitative cervicovaginal fetal fibronectin, P =.72, nor was there a difference between the women with severe preeclampsia and the controls, P = 1.0, or between the nulliparous women with preeclampsia versus the nulliparous controls, P =.3. CONCLUSION: Fetal fibronectin is not elevated in cervicovaginal secretions of women with preeclampsia.     

Criteria of pregnancy termination in women with preeclampsia

Preeclampsia remains an important cause of maternal and neonatal mortality and morbidity. Delivery is always the appropriate therapy for the mother but may be responsible for neonatal adverse outcomes, particularly when it occurs at less than < 34 weeks' gestation. In women with severe preeclampsia at < 34 weeks expectant management to improve neonatal mortality and morbidity may be performed under close monitoring of both the mother and the fetus. Any severe condition of the mother (HELLP syndrome, abruptio placentae, eclampsia) or the fetus (abnormal fetal heart rate) should lead to prompt delivery. In women with mild preeclampsia, expectant management should be performed until 38 weeks gestation.