Prostacyclin/thromboxane early changes in pregnancies that are complicated by preeclampsia

OBJECTIVE: The purpose of this study was to examine 6-keto-prostaglandin F(1)(alpha) and thromboxane B(2) plasma levels throughout normotensive and preeclamptic pregnancies and to analyze the predictive values of these quantifications for the detection of preeclampsia during the second trimester of pregnancy. STUDY DESIGN: Blood samples were collected from 30 healthy, nonpregnant women and at 4-week intervals from a cohort of nulliparous women who were recruited before 16 weeks of gestation. Preeclampsia developed in 26 patients; 52 normotensive control subjects were matched from the same cohort. The 6-keto-prostaglandin F(1)(alpha) and thromboxane B(2) were assayed by radioimmunoassay. Trends were compared between pregnancy groups and with the nonpregnant women. Predictive values were determined with the second-trimester assessments. RESULTS: The 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio decreased throughout pregnancy in women with preeclampsia; there were no significant changes in normotensive women. We found higher thromboxane B(2) levels within the group with preeclampsia during the first gestational trimester (preeclampsia, 188 +/- 17 pg/mL; control, 119 +/- 4.8 pg/mL [mean +/- SEM]; P =.001). During the third trimester, patients with preeclampsia had lower 6-keto-prostaglandin F(1)(alpha) levels than did control subjects (preeclampsia, 191 +/- 9.8 pg/mL; control, 288 +/- 10 pg/mL; P =.001). The 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio was suitable to calculate predictive values; the best cutoff point and time interval were 3.0 and 22 to 26 weeks of gestation, respectively. Sensitivity, specificity, and positive and negative predictive values were 88%, 97%, 69%, and 99%, respectively; the odds ratio was 14.6 (95% CI, 6.9-30.4). CONCLUSION: The prostacyclin/thromboxane ratio favored vasoconstriction early in gestation in women in whom preeclampsia developed. A 6-keto-prostaglandin F(1)(alpha)/thromboxane B(2) ratio of 相似文献   

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.     

Pulse pressure and risk of preeclampsia: a prospective study

OBJECTIVE: To find whether pulse pressure, a measure of arterial compliance, is associated early in pregnancy with increased risk of developing preeclampsia. METHODS: In a prospective cohort of 576 nulliparas, we examined blood pressures throughout pregnancy and at 6-8 weeks postpartum. Measurements during weeks 7-15, 16-24, and 25-38 of gestation were pooled to find averages for each period. Outcomes assessed were gestational hypertension and preeclampsia. Logistic regression analysis was used to develop relative risks and 95% confidence intervals. RESULTS: We confirmed 34 (5.9%) cases of preeclampsia, 32 (5.6%) cases of gestational hypertension, and 510 normotensive women. Mean systolic and diastolic blood pressures and mean arterial pressures were elevated throughout pregnancy in women who developed hypertensive disorders of pregnancy compared with normotensive women. Pulse pressure at 7-15 weeks was significantly higher in women who developed preeclampsia (45 +/- 6 mmHg) than in those who developed gestational hypertension (41 +/- 7 mmHg, P =.03) and normotensive women (41 +/- 8 mmHg, P =.01). Examined in tertiles, increasing pulse pressure was associated with increasing risk of developing preeclampsia (P for trend =.01) but not gestational hypertension (P for trend =.95). After adjustment for potential confounders, a 1-mmHg rise in early pregnancy pulse pressure was associated with a 6% (95% confidence interval: 1, 10) increase in risk for developing preeclampsia but not gestational hypertension (relative risk: 1%; 95% confidence interval: -1, 6). Beyond 15 weeks' gestation, differences between groups diminished, but women with any hypertensive disorder had higher pulse pressures than women with uncomplicated pregnancies. CONCLUSION: Elevated pulse pressure, indicating poor arterial compliance, was evident early in pregnancies of women who subsequently developed preeclampsia.     

Adhesion molecules changes at 20 gestation weeks in pregnancies complicated by preeclampsia

OBJECTIVES: To examine soluble E-selectin, L-selectin, P-selectin, ICAM-1, and VCAM-1 levels in normotensive and preeclamptic pregnancies. To determine cut-offs useful for preeclampsia early detection. STUDY DESIGN: A cohort of nulliparous women was recruited at family medicine clinics in Mexico City. Preeclampsia developed in 75 patients; 125 normotensive controls were matched. Adhesion molecules were assessed in serum obtained at 20 gestation weeks and in third trimester pregnancies. Predictive values and odds ratios for preeclampsia development were calculated with the 20 gestation week results. Threshold values were selected based on ROC curves values. RESULTS: In women with subsequent preeclampsia, sL-selectin and sVCAM-1 concentrations were significantly lower, whereas sE-selectin, sP-selectin and sICAM-1 levels were significantly higher, compared with controls at mid-pregnancy (p<0.05). The odds ratio for low sL-selectin was 25.6 (95% CI, 8.9-73.5; cut-off, 1414 ng/ml). The sensitivity, specificity, and positive and negative predictive values of low sL-selectin for preeclampsia development were 84, 90, 39, and 98%, respectively, whereas its sensitivity, specificity, and positive and negative predictive values for severe preeclampsia development (cut-off, 1210 ng/ml) were 100, 98, 60, and 100%, respectively. CONCLUSIONS: Early enhanced activation of endothelial cells, platelets and leukocytes seem to be present in preeclamptic patients, especially in those that develop severe preeclampsia. Low sL-selectin levels at 20 gestation weeks may be an indicator of preeclampsia development.     

血浆纤维结合蛋白对胎儿生长受限和妊娠高血压综合征的早期预测价值

目的探讨孕妇血浆纤维结合蛋白(FN)水平变化对胎儿生长受限(FGR)和妊娠高血压综合征(妊高征)的早期预测价值.方法用免疫速率比浊法测定130例孕妇血浆FN水平,并随访其妊娠结局.比较用FN水平预测FGR、妊高征、FGR合并妊高征3种妊娠结局的预测价值.结果 (1)妊娠结局130例孕妇中发生FGR 10例(FGR组)、妊高征10例(妊高征组)、FGR合并妊高征4例(FGR+妊高征组)、无合并症的正常妊娠妇女106例(正常妊娠组).4组孕妇间平均年龄、孕次、取样孕周、分娩孕周比较,差异无显著性(P＞0.05).(2)FGR组、妊高征组、FGR+妊高征组FN水平分别为(486.45±122.69) mg/L、 (428.38±118.71) mg/L、(443.66±68.13) mg/L,均显著高于正常妊娠组(284.41±93.83) mg/L(P＜0.001).(3) FN水平预测FGR 、妊高征、FGR+妊高征3种妊娠结局的受试者工作曲线(ROC曲线)下面积,分别为0.893、0.818、0.867. (4)以FN≥460 mg/L为最佳切点预测3种妊娠结局的敏感性、特异性、阳性预测值、阴性预测值及Kappa指数,FGR组为57.14%、95.69%、61.54%、94.87%、0.545 5;妊高征组为42.86%、91.38%、37.50%、92.98%、0.322 1;FGR+妊高征组为91.27%、50.00%、15.38%、98.29%、0.197 5. 结论晚孕早期妇女血浆FN水平可作为FGR或妊高征的早期预测指标之一,最佳切点为≥460 mg/L,尤其对FGR的预测价值优于对妊高征的预测.     

Cerebrospinal fluid leptin levels in preeclampsia: relation to maternal serum leptin levels

BACKGROUND: To determine whether cerebrospinal fluid (CSF) and circulating levels of leptin differ between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal serum and CSF leptin concentrations obtained in the third trimester of the gestation were compared in 16 women with mild preeclampsia and 23 normotensive pregnant women who underwent cesarean section. Before administering local anesthetic for spinal anesthesia, 2 mL CSF and 4 mL venous blood sample were taken and were stored at -30 degrees C until serum and CSF leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean CSF leptin concentrations were not significantly different between the two groups (preeclampsia 9.7 +/- 4.2 ng/mL, normotensive 13.6 +/- 4.3 ng/mL, p = 0.952). Similarly, mean serum leptin concentrations were similar between the two groups (mild preeclampsia 21.7 +/- 7.1 ng/mL, normotensive 18.3 +/- 6.7 ng/mL, p = 0.698). CSF leptin levels are inversely related to the serum leptin concentrations in preeclamptic patients (r = -0.87, p = 0.000). An inverse relationship was also detected between CSF and serum leptin levels in normotensive pregnant subjects (r = -0.66, p = 0.000). CONCLUSIONS: CSF and serum leptin levels were similar in patients with preeclampsia and normotensive pregnant women. However, the CSF leptin was negatively correlated with the serum leptin concentrations in preeclamptic and normotensive control subjects, suggesting that leptin enters the brain by a saturable transport system. Further work is needed to confirm our findings.     

Urinary calcium as an early marker for preeclampsia

Women who develop preeclampsia during pregnancy excrete less calcium than healthy pregnant women. Whether this reduction in calcium excretion precedes or follows hypertension is unknown. We prospectively measured urinary calcium excretion in 103 consecutive nulliparous women at risk for preeclampsia and presenting for prenatal care before 24 weeks' gestation. Serial 24-hour urine specimens were obtained at 10-24 weeks, 25-32 weeks, and 33 weeks to term. After delivery, the charts were reviewed for the presence of preeclampsia and gestational hypertension. At the first collection, patients who later developed preeclampsia excreted less urinary calcium (169 +/- 30 mg/24 hours; mean +/- standard error of the mean) than those who remained normotensive (298 +/- 15 mg/24 hours) (P less than .05); this reduction persisted throughout gestation. Using a receiver operator curve, we calculated a predictive threshold calcium value for hypertension of 195 mg/24 hours. The difference in the incidence of preeclampsia between pregnant women with calcium excretion values at or below 195 mg/24 hours (87%, 95% confidence interval 52-98%) and those with values above that level (2%, confidence interval 0.3-8%) was highly significant (Fisher exact test, P less than .0001). The 95% lower limit of relative risk for preeclampsia in patients with a calcium excretion equal to or below 195 mg/24 hours in the first collection was 9.4. These observations suggest a pathophysiologic role for altered urinary calcium excretion in women with preeclampsia that may contribute to the early identification of patients at risk for this disease.     

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.     

Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies

Preeclampsia is far more common in women's first pregnancy but the mechanism of this association is unknown. Altered angiogenesis, marked by increased levels of circulating soluble fms-like tyrosine kinase (sFlt-1), an inhibitor of placental growth factor (PlGF) and vascular endothelial growth factor, has been implicated in the pathogenesis of preeclampsia. We tested the hypothesis that nulliparous women demonstrate increased sFlt-1 levels compared with multiparous women, suggesting an overall increase in relative antiangiogenesis during first pregnancies. We measured sFlt-1 and PlGF levels in early pregnancy serum samples from the first 2 completed pregnancies of 97 women who participated in the MOMS cohort study. Repeated measures analyses demonstrated that sFlt-1 levels were significantly increased in first compared with second pregnancies (877+/-598 pg/mL vs 728+/-399 pg/mL; P=.01) but there was no significant difference in PlGF levels (45.3+/-40.7 pg/mL vs 40.1+/-31.9 pg/mL; P=.14). After adjusting for age, gestational age, blood pressure, body mass index, smoking, and the interpregnancy time interval, the residual decrease in sFlt-1 levels from the first to the second pregnancy remained significant at 107 pg/mL (P=.04). Significant interaction between ethnicity and pregnancy order on sFlt-1 levels was observed such that Hispanic women demonstrated greater sFlt-1 levels than white women during their first pregnancy but lower levels in their second pregnancies. Increased sFlt-1 secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Additional studies are needed to verify these findings and to further examine ethnic differences in angiogenesis factors and their potential impact on the incidence of preeclampsia.     

Low plasma levels of oxidized low density lipoprotein in preeclampsia

BACKGROUND: Markers of lipid peroxidation are commonly used to assess oxidative stress in preeclampsia. The aim of this study was to assess the concentration of oxidized low density lipoprotein (oxLDL), a novel marker for lipid peroxidation, and that of the thiobarbituric acid reactive substances (TBARS) in the pathogenesis of severe preeclampsia and to investigate the influence of gestational age on these parameters. METHOD: Plasma levels of oxLDL and TBARS were assayed in women with severe preeclampsia (n = 40), normotensive pregnant controls matched for gestational age (n = 24) and normotensive pregnant controls at full term (n = 16). RESULTS: Women with preeclampsia showed lower oxLDL levels (mean +/- SE) than matched controls (181 +/- 12 vs. 219 +/- 14; p = 0.027), whereas no differences were found for the TBARS concentration (3.8 +/- 0.6 vs. 3.7 +/- 0.4). When women with preeclampsia were compared to control women at full term, TBARS were elevated (3.8 +/- 0.6 vs. 1.5 +/- 0.2; p = 0.01). However, in women with normotensive pregnancy TBARS were also lower in full-term control pregnancy compared to early third-trimester values (p < 0.0001). CONCLUSION: Plasma TBARS decreased during the third trimester of pregnancy, underlining the importance of matching for gestational age when studying markers of lipid peroxidation in pregnant women. Women with preeclampsia had lower plasma levels of oxLDL compared to gestational age-matched controls, indicating that oxLDL could be a marker for preeclampsia.     

Maternal erythrocyte malondialdehyde level in preeclampsia prediction: a longitudinal study

We aimed to determine the value of maternal erythrocyte malondialdehyde levels in the prediction of preeclampsia. 110 healthy women were included in this prospective study. Maternal erythrocyte malondialdehyde levels were measured at each trimester of pregnancy (10-14, 20-25 and 30-35 gestational weeks). On follow-up, patients were assigned to two groups as normotensive women and preeclamptic patients. Preeclampsia had developed in eight (8.9%) of the 90 pregnant women who completed the study. Preeclamptic patients were diagnosed between 36 and 39 gestational weeks (36.8 +/- 1.0 weeks). Malondialdehyde levels of preeclamptic patients increased significantly in the third trimester (p < 0.05), while there was no difference between values of malondialdehyde in the first and second trimester. Malondialdehyde levels were significantly higher in the patients who developed preeclampsia than in those who did not in the third trimester (p < 0.05). With the use of the receiver operating characteristics (ROC) 35.98 nmol malondialdehyde/gm hemoglobin was found to be a cut-off value predictive for the development of preeclampsia in the third trimester. However, cut-off values in the first and second trimesters could not be found. The sensitivity, specificity, positive and negative predictive values were 89, 75, 29 and 98%, respectively. Preeclampsia risk was found to increase nearly 24 times in values above 35.98 nmol malondialdehyde/ gm hemoglobin. Our results showed that maternal erythrocyte malondialdehyde could predict patients within a few weeks prior to onset of clinical symptoms of preeclampsia in the third trimester. There is no evidence of enhanced early lipid peroxidation in pregnancies with late onset preeclampsia.     

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.     

Failure of serum beta2-microglobulin levels as an early marker of preeclampsia

OBJECTIVE: Our purpose was to determine whether second-trimester maternal serum beta(2)-microglobulin levels could be used to predict subsequent development of preeclampsia. STUDY DESIGN: We first did a cross-sectional study to compare serum concentrations of beta(2)-microglobulin between women with preeclampsia and normotensive women. Serum beta(2)-microglobulin concentrations of 11 consecutive patients hospitalized for preeclampsia were compared with those of 11 normotensive women hospitalized for threatened premature labor. The second part of the study consisted of a nested case-control study in which each woman in whom preeclampsia ultimately developed was matched with 2 women who remained normotensive throughout gestation. For that purpose a total of 450 consecutive healthy nulliparous women were studied prospectively. Blood samples were collected between 20 and 24.9 weeks' gestation and frozen at -20 degrees C until assay after groups had been selected. RESULTS: In the cross-sectional study serum beta(2)-microglobulin levels were significantly higher in women with preeclampsia than in control women (1.87 +/- 0.36 mg/L vs 1.01 +/- 0. 12 mg/L; t = 7.61; P <.0001). Among the 450 women who were followed up prospectively, preeclampsia developed in 7 (1.5 %). Fourteen of the women who remained normotensive were matched with the 7 women in whom preeclampsia ultimately developed. No difference was found in early serum beta(2)-microglobulin concentrations between women in whom preeclampsia subsequently developed and those who remained normotensive throughout gestation (1.02 +/- 0.12 vs 0.95 +/- 0.12 mg/L). CONCLUSIONS: Serum beta(2)-microglobulin levels do not predict subsequent preeclampsia.     

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.     

Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether serum concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a major decidual protein, at 16 weeks' gestation differ between women who later develop pregnancy-related hypertension and normotensive women. METHODS: Concentrations of IGFBP-1 were measured using immunoenzymometric assay in serum samples collected for alpha-fetoprotein (AFP) and free beta subunit of hCG (free beta-hCG) determinations in a Down syndrome screening program at 16 weeks' gestation in a population-based cohort of 1049 nulliparous women. After exclusion of subjects with multiple pregnancies, insulin-dependent diabetes, major fetal malformations, and incomplete data, 917 subjects remained eligible. RESULTS: The mean levels (+/- standard deviation) of IGFBP-1 were significantly lower in 34 women who later developed preeclampsia (73 +/- 43 microg/L, P < .01) and in 80 women with White A diabetes (84.7 +/- 53 microg/L, P < .01) compared with controls (103 +/- 58 microg/L). In seven women with White A diabetes and subsequent preeclampsia IGFBP-1 levels were especially low (41 +/- 34 microg/L). The concentrations of AFP and free beta-hCG in the subgroups with hypertensive disorders were not significantly different from those of normotensive women. CONCLUSION: Decreased IGFBP-1 levels at 16 weeks' gestation in women who develop preeclampsia might indicate impaired decidual function. Hyperinsulinemia, a known risk factor for preeclampsia, might contribute to decreased concentrations of serum IGFBP-1. However, due to low sensitivity, assay of serum IGFBP-1 was not clinically valuable for predicting preeclampsia.     

Low plasma HLA-G protein concentrations in early gestation indicate the development of preeclampsia later in pregnancy

OBJECTIVE: The aim of this study was to determine whether circulating HLA-G levels, early in pregnancy, predict the subsequent development of preeclampsia (PE). STUDY DESIGN: Plasma samples, collected longitudinally during the first, second, and third trimesters, from 12 PE patients and 12 matched control patients were tested for HLA-G protein using a validated sandwich ELISA. RESULTS: First and second trimester HLA-G levels in PE were significantly lower than in control patients (first trimester, 1.25 microg/mL vs 1.95 microg/mL, P=.029; second trimester, 1.11 microg/mL vs 1.90 microg/mL, P=.024). CONCLUSION: Our results indicate that HLA-G levels in plasma from women who subsequently develop PE are lower than control patients, as early as the first trimester. This suggests that determination of circulating HLA-G protein concentration may be useful as an early predictor for the development of PE.     

Prospective analysis of placenta growth factor (PlGF) concentrations in the plasma of women with normal pregnancy and pregnancies complicated by preeclampsia.

OBJECTIVE: The aim of this study was to analyze if levels of plasma PlGF in the second half of pregnancy have predictive value for the identification of women destined to develop preeclampsia or another complication of pregnancy. Material and METHODS: A bank of 1.543 randomly collected plasma samples (22-29 weeks of gestation) was established and PlGF concentrations were quantitated in a prospective longitudinal study in all pregnant women who developed a complication of pregnancy in late gestation (177 of 1.543) and the same number of gestational age matched pregnancies with normal outcome. RESULTS: Plasma PlGF levels in pregnant women rise steadily throughout pregnancy from the level of nonpregnant women (< 50 pg/mL) to levels exceeding 500 pg/mL after 30 weeks of gestation. Just 7.3% of pregnant women with normal outcome of pregnancy had PlGF levels of less than 200 pg/mL beyond 22 weeks of gestation (3.7% beyond 25 weeks of gestation). The rise in plasma PlGF in the second half of pregnancy was significantly attenuated in pregnancies that were complicated by preeclampsia in late gestation. Of all women who developed preeclampsia, 27.3% (12 of 44) had plasma PlGF levels below 200 pg/mL. The attenuation of the rise in plasma PlGF was not evident in other complications of pregnancy (transient hypertension, fetal retardation, pregnancy diabetes, premature contractions, proteinuria without hypertension, infections during pregnancy). CONCLUSION: The rise in plasma PlGF levels observed in normal pregnancies is significantly attenuated in pregnancies complicated by preeclampsia. Yet, due to the low sensitivity and specificity, plasma PlGF levels in the second half of pregnancy have no predictive value for the identification of individual women destined to develop preeclampsia.     

The relationship of smoking, preeclampsia, and secretory component

OBJECTIVE: We sought to determine whether total secretory component in serum is increased in women in whom preeclampsia subsequently develops. STUDY DESIGN: Serum samples were collected serially throughout pregnancy and post partum from nulliparous women (N = 1496). Serum concentrations of total secretory component were measured by an enzyme-linked immunosorbent assay in all women in whom preeclampsia developed (n = 71) and a randomly selected group of normotensive women (n = 83). RESULTS: Secretory component increased with smoking (P =.0003) and with gestation (P =.0001). In the whole group secretory component was not different in women with preeclampsia (P =.10), but there was a significant interaction of smoking, gravidity, and preeclampsia (P =.04). Among the women who smoked, secretory component was lower in women in whom preeclampsia subsequently developed compared with those who remained normotensive (P =.02). This difference was significant from 15 to 19 weeks' gestation. CONCLUSION: Very high serum concentrations of secretory component in smokers may protect against the development of preeclampsia and may indicate the involvement of mucosal tolerance.     

Total plasma fibronectin as a marker of pregnancy-induced hypertensive disorders: A longitudinal study

Objective: To determine normal values of total plasma fibronectin in all three gestational trimesters and to examine 1) whether total plasma fibronectin levels differ between normotensive, hypertensive, and preeclamptic women; and 2) whether total plasma fibronectin may serve as an early marker of pregnancy-induced hypertensive disorders.Methods: Total plasma fibronectin was measured in 376 nulliparous women once in each trimester of pregnancy. Normotensive controls (n = 222) and subjects with pregnancy-induced hypertensive disorders (n = 154) were identified after delivery. The group with pregnancy-induced hypertensive disorders was subdivided into a gestational hypertensive group (n = 125) and a preeclamptic group (n = 29). A complete total plasma fibronectin data set was obtained from 347 subjects. Trends in total plasma fibronectin values were compared for the different groups and relative risks (RRs) were calculated after optimal cutoff levels had been determined by receiver operating characteristic curves.Results: Total plasma fibronectin values (standard error of the mean) were 227 ± 3 mg/L in the first, 219 ± 3 mg/L in the second, and 260 ± 5 mg/L in the third trimesters in normotensive pregnancies. In the first trimester and persisting throughout pregnancy, total plasma fibronectin levels were significantly higher in patients with pregnancy-induced hypertensive disorders than in controls and showed a sharper increase throughout pregnancy. Increased first-trimester total plasma fibronectin levels result in an RR of 1.4 (95% confidence interval [CI] 1.1, 1.8) of developing a pregnancy-induced hypertensive disorder in general. The RR for the development of preeclampsia was 1.7 (95% CI 0.9, 3.4), which was not significant, when the first-trimester total plasma fibronectin level was above the cutoff level of 240 mg/L. The RR for developing preeclampsia was 3.8 (95% CI 1.8, 8.0) when the second-trimester total plasma fibronectin level increased above 230 mg/L.Conclusion: The findings of the present study confirm those of previous studies that have found increased total plasma fibronectin levels in pregnancy-induced hypertensive disorders. This study discovered that in these women, total plasma fibronectin levels are elevated in the first trimester. Total plasma fibronectin appears to be a poor predictor of preeclampsia when measured in a general pregnant population. Therefore, total plasma fibronectin should not be used as a routine screening test in a low-risk population. However, obstetricians may use total plasma fibronectin values to help determine the relative risk of developing pregnancy-induced hypertensive disorders.     

Anticardiolipin antibodies and the severity of preeclampsia-eclampsia.

OBJECTIVE: To identify and compare anticardiolipin antibodies (aCL) in patients with eclampsia, different grades of preeclampsia and women with normotensive pregnancy. METHODS: A cross-sectional study was conducted in 13 patients with eclampsia, 39 with preeclampsia (13 severe, 26 mild), and 52 normotensive pregnant women. All of them were studied in the 3rd trimester of pregnancy. The aCL were determined by an ELISA method. RESULTS: There were no significant differences in IgG aCL (F = 0.33, p = 0.80) and IgM aCL (F = 1.64, p = 0.18) between patients with eclampsia (6.9 +/- 3.9 U/GPL and 4.0 +/- 2.0 U/MPL), severe preeclampsia (5.7 +/- 3.5 U/GPL and 2.9 +/- 1. 3 U/MPL), mild preeclampsia (6.8 +/- 3.9 U/GPL and 2.8 +/- 1.0 U/MPL) and normotensive pregnant women (6.4 +/- 3.4 U/GPL and 3.0 +/- 1.8 U/MPL). None of the values of the aCL were considered as positive. CONCLUSION: Serum aCL levels were similar in patients with different grades of preeclampsia-eclampsia and women with normotensive pregnancy.