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.     

Serum homocysteine at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether elevated homocysteine levels precede the development of preeclampsia. METHODS: Study subjects were selected from a population-based cohort of 1049 nulliparous women from whom serum was collected for Down syndrome screening at 16 weeks' gestation. For 34 women who developed preeclampsia, 68 control women were chosen who remained normotensive. Homocysteine was analyzed by high-performance liquid chromatography and fluorescence detection. The sample size allowed detection of a 1.25-micromol/L difference at a significance level of 0.05 and the power of 0.81. RESULTS: At 16 weeks' gestation, concentrations (mean, 95% confidence interval) of homocysteine in women who developed preeclampsia, 6.99 (6.42, 7.55) micromol/L, were similar to those who remained normotensive, 6.91 (6.45, 7.34) micromol/L. CONCLUSION: Significant changes in homocysteine metabolism did not predate the appearance of clinical preeclampsia.     

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.     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白1表达与妊娠期高血压疾病发病的关系

目的探讨胰岛素样生长因子1(IGF-1)与胰岛素样生长因子结合蛋白1(IGFBP-1)在妊娠期高血压疾病发病中的作用。方法采用酶联免疫吸附法(ELISA)及免疫组化方法检测60例妊娠期高血压疾病患者(妊娠期高血压疾病组,其中妊娠期高血压20例、轻度子痫前期19例、重度子痫前期21例)及18例正常妊娠妇女(对照组)的血清及胎盘组织中IGF-1及IGFBP-1的水平,并分析妊娠期高血压疾病组患者血清中IGF-1水平与胎盘组织中IGFBP-1的相关性。结果(1)血清IGF-1水平:妊娠期高血压疾病组为(229±100)μg/L,明显低于对照组的(336±120)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者血清中IGF-1水平为(303±80)μg/L,轻度子痫前期患者为(233±77)μg/L,重度子痫前期患者为(155±73)μg/L。3者间比较,差异有统计学意义(P<0.05)。(2)胎盘组织中IGF-1阳性率:妊娠期高血压疾病组为48%(29/60),明显低于对照组的83%(15/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显低于对照组(P<0.05,P<0.01)。(3)血清中IGFBP-1水平:妊娠期高血压疾病组为(161±90)μg/L,明显高于对照组的(98±75)μg/L,两组比较,差异有统计学意义(P<0.01)。妊娠期高血压患者为(97±73)μg/L,轻度子痫前期患者为(157±69)μg/L,重度子痫前期患者为(225±81)μg/L。3者间比较,差异有统计学意义(P<0.05)。(4)胎盘组织中IGFBP-1阳性率:妊娠期高血压疾病组为77%(46/60),明显高于对照组的39%(5/18),两组比较,差异有统计学意义(P<0.01);轻、重度子痫前期患者明显高于对照组(P<0.05,P<0.01)。(5)相关性:妊娠期高血压疾病组患者血清及胎盘组织中IGF-1水平分别与相应部位的IGFBP-1水平均呈负相关(r=-0.269,P<0.05;r=-0.396,P<0.01)。血清中IGFBP-1水平与胎盘组织中IGFBP-1表达水平呈正相关(r=0.388,P<0.01)。结论孕妇血清及胎盘组织中IGF-1、IGFBP-1水平变化与妊娠期高血压疾病发病及病情发展有关。     

Estimation of oxidative products of nitric oxide (nitrates, nitrites) in preeclampsia

Oxidative products of nitric oxide, serum nitrates and nitrites were estimated in 50 primigravidas with preeclampsia and in 50 gestation and age-matched normotensive primigravidas. Thirty three (66%) of these women had mild preeclampsia and 17 (34%) had severe preeclampsia. Serum nitrate and nitrite levels were significantly higher in preeclamptic women (nitrates - 15 +/- 1.17; nitrites - 11.82 +/- 1.16 micromol/L) than in the normotensive pregnant women (nitrates 11.82 +/- 1.16; nitrites - 5.08 +/- 0.47 micromol/L, p < 0.001). In preeclamptic women, serum nitrate and nitrite levels correlated with the severity of the disease (mild preeclampsia nitrate - 14.46 +/- 1.98; nitrite 6.21 +/- 0.84 micromol/L, severe preeclampsia nitrate - 16.65 +/- 3.64; Nitrite - 6.87 +/- 1.56 micromol/L). In preeclampsia there was significant positive correlation between nitrate and nitrite levels and diastolic blood pressure and proteinuria.     

Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment.

OBJECTIVE: The purpose of this study was to determine if endothelin levels are elevated in women with preeclampsia and if these levels correlated with other laboratory features of disease severity. STUDY DESIGN: Parameters were compared in four groups of women volunteers by means of analysis of variance: (1) 16 women with preeclamptic pregnancies, (2) 11 pregnant women without preeclampsia, of similar lengths of gestation, (3) six otherwise normal women with pregnancies at term or beyond (greater than 38 weeks), and (4) 22 normotensive young women. RESULTS: Endothelin levels were elevated in women with preeclampsia as compared with those of gestation-matched pregnant and nonpregnant controls (22.6 +/- 2.0 vs 12.0 +/- 1.0 vs 10.4 +/- 1.3 pmol/L, p less than 0.005, preeclampsia vs controls) and also were increased in late gestation (17.7 +/- 2.0 pmol/L). Endothelin correlated positively with plasma levels of uric acid (r = 0.698, p less than 0.005) and inversely with creatinine clearance (r = -0.659, p less than 0.05). CONCLUSION: Circulating endothelin levels are elevated in women with preeclampsia and correlate closely with serum uric acid levels and measures of renal dysfunction. These observations suggest that endothelin may contribute to renal vasoconstriction in preeclampsia.     

Neurokinin B peptide serum levels are higher in normotensive pregnant women than in preeclamptic pregnant women

OBJECTIVES: The purpose of this study was to examine neurokinin B levels in serum from preeclamptic and normotensive and to investigate the role of neurokinin B in preeclampsia. STUDY DESIGN: Peripheral and uterine venous blood neurokinin B levels were measured in 14 normotensive and 8 preeclamptic pregnant women by radioimmunoassay. RESULTS: Neurokinin B levels in normotensive women were 4.91 +/- 2.67 nmol/L in peripheral and 5.59 +/- 2.06 nmol/L in uterine blood. In pregnant women with preeclampsia, neurokinin B levels were 2.79 +/- 1.68 nmol/L and 3.20 +/- 1.55 nmol/L, respectively. Neurokinin B levels were significantly higher in normotensive women (P=.032 in peripheral and P=.006 in uterine blood). CONCLUSIONS: Neurokinin B serum levels were higher in normotensive women. Higher neurokinin B concentrations in normotensive pregnant women may be due to the advanced gestational age and/or the result of a negative interaction of other vasoactive substances. The role of neurokinin B in preeclampsia remains to be determined.     

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.     

Maternal plasma cellular fibronectin concentrations in normal and preeclamptic pregnancies: a longitudinal study for early prediction of preeclampsia

OBJECTIVE: The purpose of this study was to examine cellular fibronectin levels throughout normotensive and preeclamptic pregnancies and to analyze its predictive value for the detection of preeclampsia within the second trimester of pregnancy. STUDY DESIGN: Blood samples were collected at 4-week intervals from 378 healthy, 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. Plasma samples were assayed for ED-B fibronectin by enzyme-linked immunosorbent assay. Trends were compared between groups. Predictive values were determined with the use of second trimester assessments. RESULTS: In both groups, fibronectin levels rose as pregnancy advanced, but in women with preeclampsia, this increase was significantly higher (94.5% vs 31.8%; P =.006). Throughout pregnancy, patients with preeclampsia exhibited significantly higher fibronectin levels than did control subjects. As early as 9 to 12 weeks of gestation, a difference was established (preeclampsia, 3.72 +/- 0.21; control, 2.94 +/- 0.22 microg/mL [mean +/- SEM]; P =.008). The best cutoff point and time interval to calculate predictive values were 3.8 microg/mL and 22 to 26 weeks of gestation, respectively. Sensitivity, specificity, and positive and negative predictive values were 73%, 87%, 29%, and 98%, respectively; the odds ratio was 16.1 (95% CI, 8.6-30.2). CONCLUSION: In women in whom clinical preeclampsia developed, endothelial damage seemed to be present since early gestation. Cellular fibronectin levels of >or=3.8 microg/mL within 22 to 26 weeks of gestation may help in the early detection of preeclampsia in healthy nulliparous women.     

Maternal circulating nitrite levels are decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.

OBJECTIVE: To evaluate whether maternal nitric oxide synthesis in pregnancies with preeclampsia is different from that in normal normotensive pregnancies. MATERIALS: Maternal circulating combined nitrate and nitrite levels or nitrite level were compared between 10 normotensive nonpregnant women, 30 normotensive pregnant women (10 first-trimester, 10 second-trimester, and 10 third-trimester pregnancies), 20 normotensive postpartum women (10 at 1 week after delivery, and 10 at 4 weeks after delivery), and 13 preeclamptic women (32 to 40 weeks' gestation). End-products of nitric oxide synthesis were measured from maternal venous blood samples using a fluorometric assay. RESULTS: Maternal circulating nitrite levels in nonpregnant women (1.13 +/- 0.22 microM) were significantly higher than those in the first-trimester pregnant women (0.68 +/- 0.13 microM), second-trimester pregnant women (0.65 +/- 0.13 microM), third-trimester pregnant women (0.48 +/- 0.17 microM), first puerperal week women (0.36 +/- 0.16 microM), and fourth puerperal week women (0.67 +/- 0.17 microM), respectively (p < 0.05). Maternal circulating nitrite level was decreased with advancing gestation, still remained low just after delivery, and was increased 4 weeks later. There was no significant difference in maternal circulating nitrite level between preeclamptic women (0.40 +/- 0.17 microM) and third-trimester pregnant women (0.48 +/- 0.17 microM). However, there were no significant differences in maternal circulating combined nitrate and nitrite levels among the groups. CONCLUSION: These results suggest that the maternal nitric oxide synthesis is not changed in normal normotensive pregnancies and pregnancies with preeclampsia. However, plasma nitrite level, which has stronger spasmolytic activity than the activity of the nitrate, was decreased in both normal normotensive pregnancies and pregnancies with preeclampsia.     

Maternal serum free beta-hCG levels in uncomplicated pregnancies at the 10th-15th week of gestation and the development of obstetric complications

OBJECTIVE: To determine if free beta-human chorionic gonadotropin (hCG) serum levels at the 10th-14th week of gestation were different in groups of women who had experienced pregnancy complications. STUDY DESIGN: The obstetric records of women who had uncomplicated pregnancies when they consented to donate blood for biochemical research purposes early in pregnancy were reviewed. Two hundred thirteen of these women had donated blood at the 10th-14th week of gestation. Of these, 135 had uneventful pregnancies and delivered at term, 19 delivered before 37 weeks'gestation, 10 had fetuses small for gestational age, 4 developed pregnancy-induced hypertension, 7 developed gestational diabetes, 10 aborted spontaneously, 4 had an intrauterine fetal death after 20 weeks' gestation, and 24 were lost to follow-up. After the clinical groups had been identified, the 213 maternal serum stored samples were thawed and free beta-hCG measured by enzyme-linked immunosorbent assay. After normalization of the data, ANOVA was used to compare mean gestational age and mean free beta-hCG levels within groups. RESULTS: The overall mean gestational age at maternal blood sampling was 12.5 weeks. All groups had similar gestational ages at blood sampling (P = .18). The overall mean free beta-hCG serum level was 18.05 mIU/mL. Only the group of women who went on to experience spontaneous abortions had significantly lower free beta-hCG lev- els (mean, 10.45 mIU/mL; P < .03) CONCLUSION: Our data suggest that of the groups with obstetric complications evaluated, only the group of women who experienced spontaneous abortions had significantly different serum levels of free beta-hCG at the 10th-14th week of gestation.     

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.     

Lymphocyte intracellular free calcium concentration is increased in preeclampsia.

OBJECTIVES: We tested 2 hypotheses: (1) Preeclampsia is characterized by an increase in intracellular free calcium concentration in lymphocytes. (2) Levels of intracellular free calcium are influenced by the calcium concentration in the extracellular milieu or by parathyroid hormone. STUDY DESIGN: Intracellular free calcium concentrations were measured in 4 groups of women: nonpregnant women (n = 25), normotensive pregnant women (n = 30), pregnant women with chronic hypertension (n = 15), and women with preeclampsia (n = 15). Intracellular free calcium concentration was measured in the basal state, at varying extracellular calcium ion concentrations, and in the presence of exogenous parathyroid hormone. RESULTS: Women with preeclampsia had the highest basal lymphocyte intracellular free calcium concentration (121 +/- 7 nmol/L, mean +/- SEM) compared with normotensive pregnant women during the third trimester (94 +/- 3 nmol/L, P <.001) and pregnant women in the third trimester with chronic hypertension (100 +/- 3 nmol/L, P <.01). During the third trimester normotensive women and women with chronic hypertension had significantly higher basal intracellular free calcium concentrations than were found in women during the first trimester. Exposure of lymphocytes to an extracellular milieu of low calcium concentration resulted in an increase in intracellular free calcium concentration. Incubation with parathyroid hormone had no effect on intracellular free calcium concentration. CONCLUSIONS: Lymphocyte intracellular free calcium concentration is increased in preeclampsia and not in chronic hypertensive pregnancy and is greater during the third trimester than during the first trimester. Extracellular calcium depletion increases lymphocyte intracellular free calcium concentration. These data support the idea that a calcium deficit leading to an increased intracellular free calcium concentration during late pregnancy contributes to the pathogenesis of preeclampsia.     

Plasma and placental levels of interleukin-10, transforming growth factor-beta1, and epithelial-cadherin in preeclampsia

OBJECTIVE: To investigate the plasma and placental levels of interleukin-10 (IL-10), transforming growth factor-beta1 (TGF-beta1), and epithelial-cadherin (E-cadherin) in normotensive and preeclamptic pregnancies. METHODS: The study population consisted of 33 women with normotensive pregnancy and 35 women with preeclampsia. Peripheral venous blood samples were collected before labor (35.3 +/- 1.1 and 34.2 +/- 3.4 weeks' gestation for normotensive and preeclamptic pregnancies, respectively), and placental tissues were obtained after delivery. Maternal plasma and placental homogenate IL-10, TGF-beta1, and E-cadherin levels were determined by enzyme-linked immunosorbent assay. RESULTS: The mean plasma and placental levels of IL-10, TGF-beta1, and E-cadherin were significantly higher in preeclamptic than normotensive patients (P <.001). The plasma and placental levels of IL-10, TGF-beta1, and E-cadherin significantly increased with the increments in diastolic blood pressure (P <.001). CONCLUSION: IL-10, TGF-beta1, and E-cadherin may be involved in the pathologic process of preeclampsia. The pathophysiologic changes associated with preeclampsia may stem in part from the overproduction of these placental mediators.     

Risks of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes mellitus. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units

OBJECTIVES: This study was undertaken to determine the frequencies of preeclampsia and adverse neonatal outcomes among women with pregestational diabetes. STUDY DESIGN: This was a prospective observation of pregnancy outcomes among 462 women with pregestational diabetes mellitus (White classes B-F) and singleton pregnancies who were enrolled in a multicenter trial to compare low-dose aspirin with placebo for preeclampsia prevention. The main outcome measures were preeclampsia and neonatal outcomes. RESULTS: Among 462 women with pregestational diabetes, 92 (20%) had preeclampsia. Preeclampsia frequency rose significantly with increasing severity of diabetes according to White classification (class B, 11%; class C, 22%; class D, 21%; class R plus class F, 36%; P <.0001). Preeclampsia was also more common among women who had proteinuria at baseline (28% vs 18%; odds ratio, 1.75; 95% confidence interval, 1.02-3.01). Frequency of preterm delivery at <35 weeks' gestation rose greatly with increasing severity of diabetes (P =.0002). Women with proteinuria at baseline were significantly more likely to be delivered at <35 weeks' gestation (29% vs 13%; odds ratio, 2.6; 95% confidence interval, 1.5-4.6) and to have small-for-gestational-age infants (14% vs 3%; odds ratio, 5. 4; 95% confidence interval, 2.7-17.7), and they were less likely to have large-for-gestational-age infants (14% vs 40%; odds ratio, 0.2; 95% confidence interval, 0.1-0.5). CONCLUSION: Among women with pregestational diabetes mellitus, the frequency of preeclampsia rose with increasing severity of diabetes. Proteinuria early in pregnancy was associated with marked increases in adverse neonatal outcomes independent of preeclampsia development.     

Serum insulin, insulin-like growth factor-I, and insulin-like growth factor binding protein-1 in women who develop preeclampsia

OBJECTIVE: To determine whether second-trimester serum concentrations of insulin, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-1 (IGFBP-1) were altered in women before they developed clinical signs of preeclampsia. METHODS: A nested case-control study used serum obtained during second-trimester pregnancies from 12 women who developed preeclampsia matched with 24 controls who remained normotensive. Nine preeclamptic subjects and 18 controls were necessary to have 80% power to discern a 20% difference between groups with regard to the analytes under consideration. RESULTS: There were no significant differences between cases and controls with respect to many demographic factors. Women who developed preeclampsia had insulin concentrations that were not significantly different from controls, but serum concentrations of IGF-I were significantly higher and IGFBP-1 were significantly lower than those of the controls. The IGF-I/IGFBP-1 ratio helped to identify those at risk for developing preeclampsia. CONCLUSIONS: Serum concentrations of IGF-I and IGFBP-1 were abnormal long before women manifested clinical evidence of preeclampsia in this study. These alterations might be related to abnormalities in trophoblastic invasion and prove useful as potential markers for the identification of women who are at high risk of developing preeclampsia.     

Risk factors for placenta accreta

OBJECTIVE: To identify risk factors associated with placenta accreta in a large cohort study. METHODS: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14-22 weeks' gestation using alpha-fetoprotein (AFP) and free beta-hCG between January 1994 and June 1997, and delivered in the same institution, were included (n = 10,672). Those who had multiple gestations (n = 200), overt diabetes (n = 11), or fetal malformations (n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis (n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation (n = 26) or histologic confirmation (n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. RESULTS: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free beta-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. CONCLUSION: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free beta-hCG levels, and advanced maternal age.     

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.     

Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia

OBJECTIVE: To study the plasma levels of homocysteine in preeclampsia and relate them to insulin sensitivity. METHODS: In association with a 3-hour intravenous glucose-tolerance test (glucose 0.3 g/kg at 0 and 0.03 IU insulin 20 minutes later), we measured plasma levels of homocysteine, vitamin B12, and folic acid in 22 women with preeclampsia and 16 controls between 29 and 39 weeks' gestation. In 14 women with preeclampsia and 11 controls, plasma samples also were collected 3 months after delivery. RESULTS: Levels of homocysteine in women with preeclampsia (6.7 +/- 0.4 micromol/L, mean +/- standard error) were higher (P < .001) than those in controls (3.8 +/- 0.2 micromol/L) and related significantly to the level of proteinuria (r = .49, P = .02). Vitamin B12 concentrations were lower in women with preeclampsia (166.0 +/- 10.4 compared with 212.4 +/- 16.4 pmol/L, P = .02), whereas levels of folic acid showed no difference between the groups. After delivery, levels of homocysteine increased to 9.1 +/- 0.6 and 8.2 +/- 0.6 micromol/L in women with preeclampsia and controls, vitamin B12 increased to 298.8 +/- 28.6 compared with 334.9 +/- 24.0 pmol/l, and folic acid decreased to 10.6 +/- 2.0 compared with 7.9 +/- 0.8 nmol/L, with no difference emerging between the groups. In women with preeclampsia but not in controls, plasma homocysteine was negatively related to insulin sensitivity (r = -.51, P = .02). The mean 2.9-fold increase in glucose or 52.5-fold increase in insulin during the insulin-sensitivity test failed to affect homocysteine levels. CONCLUSION: Women with preeclampsia have high plasma homocysteine levels that are inversely related to insulin sensitivity.