Elevated plasma homocysteine in early pregnancy: a risk factor for the development of severe preeclampsia

OBJECTIVE: The aim of our study was to determine if an elevated plasma homocysteine level in early pregnancy is associated with the development of severe preeclampsia. STUDY DESIGN: Blood samples were obtained from patients attending their first antenatal visit. Cases were asymptomatic women who subsequently developed severe preeclampsia. Controls were matched for gestational age and date of sample collection. Plasma homocysteine level was measured by using fluorescence polarization immunoassay. RESULTS: There were 56 patients with severe preeclampsia from whom blood samples were obtained at a mean (+/-SD) gestation of 15.3 weeks (+/-4.04 weeks) and 112 controls at 14.9 weeks (+/-3.41 weeks). The preeclampsia cases had a mean (+/-SD) homocysteine level of 9.8 micromol/L (+/-3.3 micromol/L), whereas controls had a mean homocysteine level of 8.4 micromol/L (+/-1.9 micromol/L), P < or = .0001. CONCLUSION: Women who develop severe preeclampsia have higher plasma homocysteine levels in early pregnancy than women who remain normotensive throughout pregnancy. An elevated plasma homocysteine level in early pregnancy can increase the risk of developing severe preeclampsia by almost threefold.     

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.     

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.     

Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction

OBJECTIVE: The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension, preeclampsia, or intrauterine growth restriction. STUDY DESIGN: Women with normal but relatively low plasma zinc levels were randomly assigned to receive zinc supplementation or placebo from 19 weeks' gestation until delivery. Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored samples (zinc group, 231/294; placebo group, 206/286) at 26 and 37 weeks' gestation. Among all women with available samples, pregnancy-induced hypertension (n = 12) or preeclampsia (n = 4) developed in 16 women, and 22 pregnancies were complicated by intrauterine growth restriction. RESULTS: Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks' gestation but were significantly higher at 37 weeks' gestation. Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points. CONCLUSION: Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.     

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.     

Plasma thiol status in preeclampsia

OBJECTIVE: To measure plasma thiol levels in women with normal pregnancies, women with preeclampsia, and nonpregnant controls to define plasma thiol's effect on glutathione homeostasis and pathophysiology of preeclampsia. METHODS: Total plasma cysteine, gamma-glutamylcysteine, homocysteine, cysteinylglycine, and glutathione levels were measured in ten nonpregnant women, ten women with normotensive pregnancies, and 20 women with preeclampsia at delivery. RESULTS: Median total plasma levels of all thiols in normotensive pregnant women were significantly lower than in nonpregnant women. Median total plasma cysteine and homocysteine levels in women with preeclampsia were significantly higher compared with pregnant controls (254 versus 190 micromol/L, P < .001; and 13.3 versus 8.4 micromol/L, P < .02, respectively), whereas glutathione levels were significantly lower in women with preeclampsia compared with those in pregnant controls (5.1 versus 6.3 micromol/L, P < .05). CONCLUSION: In women with preeclampsia, homocysteine and cysteine levels, which are lowered in normotensive pregnancy, were comparable to levels in nonpregnant women, whereas glutathione levels were lower. Those results suggest that in women with preeclampsia, glutathione use is higher or its synthesis is disturbed. Therefore, glutathione might affect pathophysiology of 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.     

Plasma homocyst(e)ine concentrations in eclamptic and preeclamptic African women postpartum.

OBJECTIVE: To examine the relationship between plasma homocyst(e)ine and risk of eclampsia and preeclampsia among sub-Saharan African women who delivered at Harare Maternity Hospital in Zimbabwe. METHODS: We ran a hospital-based, case-control study at Harare Maternity Hospital, University of Zimbabwe, Harare, Zimbabwe comprising 33 pregnant women with eclampsia and 138 with preeclampsia. Controls were 185 normotensive pregnant women. Plasma was collected postpartum and homocyst(e)ine levels were measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Women with eclampsia or preeclampsia had significantly higher mean homocyst(e)ine levels than normotensive controls (12.54 or 12.77 micromol/L versus 9.93 micromol/L, respectively, P<.001). The odds ratio (OR) for eclampsia was 6.03 among women in the highest quartile of the control homocyst(e)ine distribution (median 13.9 micromol/L) compared with women in the lowest quartile (median 6.2 micromol/L). The corresponding OR for preeclampsia was 4.57. Nulliparas with elevated homocyst(e)ine had a 12.90 times higher risk of preeclampsia compared with multiparas without elevated homocyst(e)ine. CONCLUSION: Postpartum plasma homocyst(e)ine concentrations are higher among Zimbabwean women with eclampsia and preeclampsia compared with normotensive women.     

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.     

Uterine artery Doppler and mid-trimester maternal plasma homocysteine in subsequent pre-eclampsia.

OBJECTIVE: To investigate whether mid-trimester maternal plasma homocysteine concentration is elevated in women who develop pre-eclampsia and in those women identified at high risk by abnormal uterine artery Doppler examination. METHODS: This was a multicenter study involving healthy women undergoing screening for pre-eclampsia by uterine artery Doppler velocimetry at 22-24 weeks' gestation. Abnormal uterine artery blood flow was defined as a mean pulsatility index (PI) above the 95th centile (1.6). Controls (mean PI < 1.6) were matched for gestational age and date of blood sample collection. Maternal plasma homocysteine concentration was measured retrospectively using a chemiluminescent immunoassay. RESULTS: In total, 683 women were recruited. Maternal plasma homocysteine concentration did not vary with gestation. Maternal plasma homocysteine concentration in women who subsequently developed pre-eclampsia (n = 80, 12%) was not significantly different from women with uncomplicated pregnancies (n = 536, 78%) (median 5.1, range 2.7-14.1 micromol/l vs. median 5.5, range 1.9-27.9 micromol/l, p = 0.44). There were no significant differences in the maternal plasma homocysteine concentration in women with abnormal uterine artery Doppler findings (n = 275) compared with controls (n = 408), (median 5.6, range 2.6-17.7 micromol/l vs. median 5.4, range 1.9-27.9 micromol/l, p = 0.13). CONCLUSION: Mid-trimester maternal plasma homocysteine concentration is not elevated in women who developed pre-eclampsia even in those at high risk defined by abnormal uterine artery Doppler velocimetry.     

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.     

Hypertensive disorders in twin versus singleton gestations. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units

OBJECTIVE: This study was undertaken to compare rates and severity of gestational hypertension and preeclampsia, as well as perinatal outcomes when these complications develop, between women with twin gestations and those with singleton gestations. STUDY DESIGN: This was a secondary analysis of prospective data from women with twin (n = 684) and singleton (n = 2946) gestations enrolled in two separate multicenter trials of low-dose aspirin for prevention of preeclampsia. End points were rates of gestational hypertension, rates of preeclampsia, and perinatal outcomes among women with hypertensive disorders. RESULTS: Women with twin gestations had higher rates of gestational hypertension (relative risk, 2.04; 95% confidence interval, 1.60-2.59) and preeclampsia (relative risk, 2. 62; 95% confidence interval, 2.03-3.38). In addition, women with gestational hypertension during twin gestations had higher rates of preterm delivery at both <37 weeks' gestation (51.1% vs 5.9%; P <. 0001) and <35 weeks' gestation (18.2% vs 1.6%; P <.0001) and also had higher rates of small-for-gestational-age infants (14.8% vs 7. 0%; P =.04). Moreover, when outcomes associated with preeclampsia were compared, women with twin gestations had significantly higher rates of preterm delivery at <37 weeks' gestation (66.7% vs 19.6%; P <.0001), preterm delivery at <35 weeks' gestation (34.5% vs 6.3%; P <.0001), and abruptio placentae (4.7% vs 0.7%; P =.07). In contrast, among women with twin pregnancies, those who remained normotensive had more adverse neonatal outcomes than did those in whom hypertensive complications developed. CONCLUSIONS: Rates for both gestational hypertension and preeclampsia are significantly higher among women with twin gestations than among those with singleton gestations. Moreover, women with twin pregnancies and hypertensive complications have higher rates of adverse neonatal outcomes than do those with singleton pregnancies.     

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.     

Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia.

OBJECTIVE: The current literature emphasizes increased risk of adverse outcomes in the presence of proteinuria and hypertension. The objective of this study was to compare the frequency of adverse fetal outcomes in women who developed hypertensive disorders with or without proteinuria. STUDY DESIGN: The study design was a secondary analysis of data from women who had preeclampsia in a previous pregnancy (n = 598) who were enrolled in a multicenter trial of aspirin for the prevention of preeclampsia. The women had no history of chronic hypertension or renal disease and were normotensive at study inclusion. The maternal and perinatal outcome variables assessed were preterm delivery at <37 and <35 weeks of gestation, rate of small-for-gestational-age infants, and abruptio placenta. Data were analyzed by using the chi-square test, and women who remained normotensive or who had mild gestational hypertension were considered as a single group because they had similar outcomes. RESULTS: As compared to mild preeclampsia, women who developed severe gestational hypertension (without proteinuria) had higher rates of both preterm delivery at <37 weeks of gestation and small-for-gestational-age infants. In addition, when compared to women with mild preeclampsia, for women with severe gestational hypertension, gestational age and birth weight were significantly lower at delivery (P <.003 for both age and birth weight). Moreover, women who developed severe gestational hypertension had higher rates of preterm delivery at <37 weeks of gestation (54.2% vs 17.8%, P =.001) and at <35 weeks of gestation (25.0% vs 8.4%, P =.0161), and delivery of small-for-gestational-age infants (20.8% vs 6.5%, P =.024) when compared to women who remained normotensive or those who developed mild gestational hypertension. There were no statistically significant differences in perinatal outcomes between the normotensive/mild gestational hypertension and the mild preeclampsia groups. Overall, women who had severe gestational hypertension had increased rates of preterm delivery and delivery of small-for-gestational-age infants than women with mild gestational hypertension or mild preeclampsia. In the presence of severe hypertension, proteinuria did not increase the rates of preterm delivery or delivery of small-for-gestational-age infants. CONCLUSIONS: In women who have gestational hypertension or preeclampsia, increased rates of preterm delivery and delivery of small-for-gestational-age infants are present only in those with severe hypertension. In these women, the presence of proteinuria does not influence perinatal outcome.     

Homocysteine plasma concentration levels for the prediction of preeclampsia in women with chronic hypertension

OBJECTIVE: The purpose of this study was to evaluate prospectively midtrimester homocysteine concentration levels for the prediction of superimposed preeclampsia in women with chronic hypertension. STUDY DESIGN: Between March 1, 2000, and February 1, 2002, pregnancies that were complicated by chronic hypertension that required medication had homocysteine, vitamin B(12), and folate concentrations measured between 16 and 20 weeks of gestation. All women received folate supplementation. An upper limit threshold for increased homocysteine was defined as the mean value plus 2 SDs. RESULTS: Fifty-seven women were enrolled. Mean homocysteine concentration levels were 5.1+/-1.7 micromo/L for the 16 women who had preeclampsia compared with 4.7+/-1.3 micromo/L for the 41 women without preeclampsia (P=.56). Two of 16 women with preeclampsia (13%) had concentration levels that exceeded the 95th percentile (6.9 micromo/L) compared with 2 of 41 women (5%) without preeclampsia (P=.31). The sensitivity and specificity were 13% (95% CI, 1.6-38.3) and 95.1% (95% CI, 83.5-99.4), respectively. CONCLUSION: Second-trimester homocysteine concentration levels were not helpful in the prediction of preeclampsia in chronically hypertensive women.     

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.     

Elevated plasma homocysteine in early pregnancy: a risk factor for the development of nonsevere preeclampsia

OBJECTIVE: We have recently demonstrated that an elevated plasma homocysteine in early pregnancy is associated with the development of severe preeclampsia. The aim of this study was to determine whether an elevated plasma homocysteine in early pregnancy is also associated with the development of nonsevere preeclampsia.STUDY DESIGN: Blood was obtained from patients attending for a first antenatal visit. Subjects were asymptomatic women who subsequently developed nonsevere preeclampsia. Controls were matched for parity, gestational age, and date of sample collection. Plasma homocysteine was measured using fluorescence polarization immunoassay.RESULTS: There were 71 cases of nonsevere preeclampsia sampled at a mean gestational age (±SD) of 15.9±3.6 weeks and 142 controls at 15.6±3.4 weeks. The preeclampsia cases had a mean (±SD) homocysteine level of 8.4±2.4 μmol/L, whereas controls had a mean homocysteine of 7.07±1.5 μmol/L (P≤.0001).CONCLUSION: Women who develop nonsevere preeclampsia have higher plasma homocysteine levels in early pregnancy compared with women who remain normotensive throughout pregnancy. An elevated plasma homocysteine value in early pregnancy may be associated with a 4-fold increased risk for development of nonsevere preeclampsia.     

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.     

ICAM-1 in maternal serum and amniotic fluid as an early marker of preeclampsia and IUGR

OBJECTIVE: To determine if plasma and amniotic fluid levels of intercellular adhesion molecule-1 (ICAM-1) at 16 weeks' gestation could be predictive of preeclampsia or intrauterine growth retardation (IUGR). STUDY DESIGN: A retrospective analysis was undertaken in 44 serum samples stored for Down's syndrome screening at 16 weeks' gestation and 44 amniotic fluid samples obtained by midtrimester amniocentesis. RESULTS: No significant difference was found between women who subsequently developed preeclampsia or IUGR and the control group. CONCLUSION: This study failed to demonstrate that ICAM-1 may be an early serum marker of preeclampsia or an amniotic fluid marker of IUGR.     

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