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.     

Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus.

OBJECTIVE: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients. PATIENTS AND METHODS: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay. RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Plasma levels of vitamin E in pregnant women prior to the development of preeclampsia and other hypertensive complications

Our aim was to investigate whether decreased levels of vitamin E can be measured during the early stages of pregnancy in women at risk of developing preeclampsia or other associated complications before the onset of the clinical syndrome. We prospectively measured the plasma concentrations of vitamin E in 62 pregnant women at 7-32 weeks of gestation who were at risk of developing preeclampsia and other complications, before the appearance of clinical signs. The results were compared with those of 16 healthy controls. Of the 62 study patients, 8 (13%) developed preeclampsia, and 18 (29%) had other complications, such as intrauterine growth restriction (n = 8), fetal or neonatal loss (n = 9), and preterm delivery (< or = 30 weeks of gestation; n = 7). Both gestational age at delivery and birth weight were significantly lower in the patients with complications than in the healthy controls. However, there were no significant differences in vitamin E levels between women who developed preeclampsia or other complications and those who did not. There was no significant correlation between plasma vitamin E and creatinine concentrations. A significant positive correlation was found in both the complicated and normal pregnancies between plasma vitamin E concentration and gestational week of blood collection (R = 0.485, p < 0.001, and R = 0.718, p = 0.004, respectively). We conclude that the vitamin E concentrations are not decreased prior to the development of preeclampsia or other complications in women at risk.     

Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women

Objective: The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. Patients and methods: The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Results: Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2?±?4.3 ng/ml in the IUGR group, 14.1?±?3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1?±?3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6?±?3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Conclusions: Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.     

Evaluation of maternal and umbilical serum TNFα levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus

Objective.?The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFα serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients.

Patients and methods.?The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFα concentrations were estimated using a sandwich ELISA assay.

Results and conclusions.?Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFα levels than those in the normotensive controls. Our findings and other reports indicate that TNFα may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor α (TNFα) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental–fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.     

Preeclampsia is associated with reduced serum levels of placenta growth factor

Objectives: Adequate vascular development of the placental bed is essential for normal pregnancy. We assessed serum levels of placenta growth factor, an angiogenic factor, throughout normal pregnancy and determined its association with preeclampsia. Study Design: Serum samples were collected from (1) 308 healthy pregnant women throughout normal gestation, (2) at delivery from 30 each gestational age–matched patients with normal pregnancy and preeclampsia, and (3) maternal and cord blood samples from normal deliveries with and without labor (n = 37 each). Placenta growth factor levels were determined with an antigen-capture enzyme-linked immunosorbent assay. Results: Maternal placenta growth factor levels during normal pregnancy increased from the first trimester to the late second trimester; they subsequently declined from 30 weeks’ gestation to delivery. Significantly less maternal placenta growth factor (P < .0001) was found in pregnancies complicated by preeclampsia, and labor significantly lowered placenta growth factor levels in both maternal (P = .0189) and cord serum samples (P < .0001). Conclusion: Decreased levels of placenta growth factor during preeclampsia could influence endothelial cell and trophoblast function, thereby contributing to the pathogenesis of the disease. (Am J Obstet Gynecol 1998;179:1539-44.)     

Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth

OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum obtained by umbilical cord sampling at delivery is correlated with fetal growth. We also estimated whether transforming growth factor-beta1 is correlated with insulin-like growth factor-I and insulin-like growth factor binding protein-1, which have been shown to correlate with fetal growth. METHODS: The active form of transforming growth factor-beta1 was analyzed in serum from cord blood from 68 fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth restriction, 15 had intrauterine growth restriction alone, and seven had fetuses that were large for gestational age (LGA). Twenty pregnancies with fetuses appropriate for gestational age (AGA) served as controls. RESULTS: Transforming growth factor-beta1 concentrations were significantly correlated with birth weight. The average transforming growth factor-beta1 concentration in the following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L; intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L; preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA, 30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor-beta1 levels were significantly lower in pregnancies complicated by intrauterine growth restriction and showed a positive correlation with birth weight (r = 0.48, P <.001). Furthermore, there was a positive correlation between insulin-like growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative correlation between insulin-like growth factor binding protein-1 and birth weight (r = -0.32, P <.01). There was also a correlation between transforming growth factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between transforming growth factor-beta1 and insulin-like growth factor binding protein-1 (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be related to fetal growth in pregnancy. The results also support previous data showing that insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to fetal growth.     

Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction

BACKGROUND: Elevated circulating homocysteine is an independent risk factor for cardiovascular disease. Increased homocysteine plasma levels have been reported to occur in approximately 20-30% of women with preeclampsia and it has been suggested that they may predict the subsequent development of preeclampsia. METHODS: In a cohort of 1874 pregnant women followed longitudinally, who participated in the Down screening program, 27 developed preeclampsia and 36 intrauterine growth restriction (IUGR). A control group of 63 uneventful pregnancies was selected. Plasma homocysteine was assayed in the early second trimester and at delivery in all groups. Data were compared with Wilcoxon's matched-pair test. RESULTS: No statistically significant difference of plasma homocysteine between controls and preeclamptic or IUGR pregnancies in the early second trimester were found. There was a significant difference, only at delivery, between the preeclamptic subjects and the controls. CONCLUSIONS: We failed to demonstrate a plasma homocysteine predictive value in pregnancies subsequently complicated by preeclampsia and IUGR. As previously stated, we found that an elevated homocysteine plasma level is associated with overt preeclampsia.     

Maternal soluble human leukocyte antigen-G levels in pregnancies complicated by foetal intrauterine growth restriction with and without preeclampsia

ObjectiveThe aim of this study was to investigate the maternal serum of soluble human leukocyte antigen-G (sHLA-G) levels in pregnant women with an isolated intrauterine growth restricted foetus (IUGR) and in preeclamptic pregnancies with and without IUGR.Patients and methodsThe study was conducted on 31 normotensive patients with pregnancy complicated by IUGR, 17 preeclamptic patients with appropriate-for-gestational-age foetal intrauterine growth, 21 with preeclampsia complicated by IUGR, and 32 healthy pregnant controls. Maternal serum sHLA-G levels were calculated using the enzyme-linked immunosorbent assay.ResultsMaternal serum sHLA-G levels tended to be higher in both groups of preeclamptic patients, and were highest in patients with IUGR in the course of severe preeclampsia. Lower serum levels of sHLA-G were observed in the group of normotensive pregnant women with an intrauterine growth restricted foetus, but these differences were not statistically significant. The mean values were 22.759 ± 14.151 units/mL in the IUGR group, 25.948 ± 18.888 units/mL in preeclamptic patients with normal intrauterine foetal growth, 31.646 ± 27.576 units/mL in preeclamptic pregnant women with IUGR, and 24.178 ± 24.828 units/mL in the healthy controls.ConclusionsOur findings suggest that the increased levels of sHLA-G in the maternal serum may play a significant role in the pathogenesis of preeclampsia, especially in preeclampsia complicated by intrauterine foetal growth restriction. These associations may offer a better insight into the etiology and pathogenesis of preeclampsia with and without IUGR. It seems that sHLA-G does not play a clinically significant role in the pathogenesis of isolated intrauterine foetal growth restriction in normotensive pregnancies.     

Soluble HLA-DR levels in the maternal circulation of normal and pathologic pregnancy

OBJECTIVE: The purpose of this study was to determine that circulating HLA-DR molecules are important candidates for the monitoring of maternal immunostimulation and immunosuppression. STUDY DESIGN: Concentrations of soluble HLA-DR molecules were estimated in EDTA plasma samples of 61 nonpregnant women, 123 healthy pregnant women in the second trimester, 66 healthy women who were delivered at term, and 136 women who were delivered because of complications such as uncontrollable preterm intrauterine activation, abruptio placentae, intrauterine growth retardation, preeclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. RESULTS: In comparison to nonpregnant women, the normal course of pregnancy was associated with strongly increasing levels of soluble HLA-DR from second trimester on until term. In comparison to women who were delivered preterm because of uncontrollable intrauterine activation, increased soluble HLA-DR concentrations were detected in case of HELLP syndrome (P <.05), although decreased levels were detected in the case of intrauterine growth retardation, preeclampsia (P <.01), and abruptio placentae (P <.01). CONCLUSION: Dysregulation of the maternal immune response to pregnancy may play an important role in the cause of complicated pregnancies.     

A prospective study on the occurrence of autoantibodies in low-risk pregnancies

OBJECTIVE: This investigation was done to study the prevalence of anti-nuclear antibodies (ANA), anti-cardiolipin antibodies (aCL), and rheumatoid factor (RF), in presumed healthy women during their pregnancies. STUDY DESIGN: During an 18 month period blood samples were taken in the first, second and third trimester from 1200 pregnant women, representing a low-risk population. Clinical data on the pregnancy outcome were obtained by birth statistics after their deliveries. The diagnoses of preeclampsia, intrauterine growth retardation, fetal death, or abruptio placentae were stated in 57 of these women. An age- and parity-matched control group of 207 women with normal pregnancy outcome was drawn from the same low-risk population (n= 1200). A nonpregnant control group consisted of 157 women. The prevalence of ANA (immunofluorescence microscopy on HEp-2 cells), aCL-immunoglobulin G (enzyme-linked immunosorbent assay), and RF (latex agglutination test) in preeclampsia, intrauterine growth retardation, fetal death, or abruptio placentae were compared to the normal pregnancies, and to the nonpregnant controls. RESULTS: ANA occurred significantly more often (P<0.05) in pregnancies complicated by preeclampsia when compared to normal pregnancies. aCL occurred sparsely in normal as well as complicated pregnancies. RF was infrequently seen among all women in this study. CONCLUSION: An association was noted between the occurrence of ANA and preeclampsia. However, this association was too insensitive to use as a clinical tool.     

Elevation in erythroblast count in maternal blood before the onset of preeclampsia

OBJECTIVE: We recently showed that both maternal and fetal erythroblast counts are elevated in the peripheral blood of pregnant women with preeclampsia. The purpose of this study was to examine whether this elevation actually occurs before the clinical onset of the disorder. STUDY DESIGN: Erythroblasts were enriched and enumerated in 97 maternal blood samples obtained in the second trimester, and results were subsequently correlated with pregnancy outcomes. RESULTS: Significantly higher quantities of erythroblasts (mean, 6041.7 vs 928.9; P =.008) were detected in blood samples obtained from women who later acquired preeclampsia (n = 15) than in blood samples from the control cohort (n = 72). Intrauterine growth restriction (n = 10) was not accompanied by a similar rise in erythroblast count. CONCLUSION: Because a large proportion of the erythroblasts in maternal blood are fetal, our data suggest that fetal-maternal cell traffic is affected early in pregnancies that are later complicated by preeclampsia but not in those affected only by intrauterine growth restriction.     

Umbilical sP-selectin levels are different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus

Objective.?The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies.

Patients and methods. The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria).

Results.?Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008?±?625.703?ng/ml in group P, 275.873?±?174.339?ng/ml in group PI, and 288.719?±?199.039?ng/ml in the control group, respectively.

Conclusions.?Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.     

Investigation of adhesion molecules (sVCAM-1) in serum of nonpregnant women, normotensive pregnant women and in patients with pregnancy complications]

OBJECTIVE: An increased expression of endothelial adhesion molecules combined with neutrophil activation in the placental bed is to be assumed aetiopathogenetically relevant in preeclampsia. MATERIAL AND METHODS: Ranges of sVCAM-1 serum concentrations of both control persons (29 nonpregnant and 25 normotensive pregnant women) and patients with different complications of pregnancy (HELLP-syndrome n = 10, preeclampsia n = 12, gestational hypertension n = 38, diabetes n = 24, growth retardation n = 21) were determined by means of ELISA. Frozen placental samples of 5 normotensive and 10 hypertensive pregnant women were investigated immunhistochemically to study the distribution of VCAM-1 in the placenta. RESULTS: Significantly elevated sVCAM-1 serum levels (p < 0.05) were identified in samples of patients with HELLP syndrome, preeclampsia, diabetes and gestational hypertension compared with serum levels of normotensive pregnant women. The cut-off level (97.5% percentile of normotensive serum levels) was calculated (775 ng/ml). VCAM-1 was localized immunhistochemically at capillaries of villi and main villi. CONCLUSIONS: There are closed relations between elevated serum levels of sVCAM-1 during pregnancy and diseases with vasculopathies of placental bed.     

Plasma hepatocyte growth factor as a marker for small-for-gestational age fetuses

OBJECTIVE: To study the association between hepatocyte growth factor (HGF) levels and pregnancy outcome. STUDY DESIGN: Hepatocyte growth factor levels were measured in 42 plasma samples between weeks 14 and 21 of gestation using an enzyme-linked immunosorbent assay (ELISA). Results were correlated to pregnancy outcome and Mann-Whitney U-test applied to study the differences. RESULTS: Hepatocyte growth factor values in pregnancies that develop preeclampsia (n=12) were not significantly different from unaffected pregnancies (n=21, multiples of the median (MoM)=1.38, P=0.47). However, hepatocyte growth factor values were significantly elevated in pregnancies of small-for-gestational age (SGA) fetuses (n=9) compared to uncomplicated pregnancies (MoM=2.66, P<0.001). CONCLUSION: Measurement of hepatocyte growth factor in peripheral blood between 14 and 21 weeks gestation may offer new possibilities in the early diagnosis and prediction of fetal birth weight but not of preeclampsia.     

Asymmetric dimethylarginine in normotensive pregnant women with isolated fetal intrauterine growth restriction: a comparison with preeclamptic women with and without intrauterine growth restriction

Objective.?The aim of this study was to evaluate maternal asymmetric dimethylarginine (ADMA) levels in pregnancies complicated by isolated fetal intrauterine growth restriction (IUGR), in preeclamptic pregnancies with and without IUGR, and in healthy normotensive pregnant women with proper weight fetuses.

Patients and methods.?The study was carried out on 54 normotensive pregnant patients with pregnancy complicated by IUGR, 35 patients with IUGR in the course of preeclampsia, 29 preeclamptic patients with appropriate-for-gestational-age weight infants and 54 healthy normotensive pregnant patients. The ADMA concentrations were evaluated using an ELISA assay.

Results.?The preeclamptic women and normotensive patients with pregnancy complicated by isolated IUGR revealed higher levels of maternal serum ADMA. The mean values of maternal serum ADMA were 0.5730?±?0.1769?μmol/l in the P group, 0.5727?±?0.1756?μmol/l in the PI group, 0.6129?±?0.1517?μmol/l in the IUGR group, and 0.5017?±?0.1116?μmol/l in the control group. The levels of ADMA were additionally higher in the patients with HELLP syndrome and in patients with pregnancy complicated by eclampsia.

Conclusions.?It seems that ADMA is an active agent not only in preeclamptic patients, but also in normotensive pregnant women with isolated fetal IUGR and could be a marker of severity of preeclampsia.     

Fibrinolytic parameters in normotensive pregnancy with intrauterine fetal growth retardation and in severe preeclampsia

In pregnancy a decrease in fibrinolytic activity, which is due to an increase in plasminogen activator inhibitor activity and plasminogen activator inhibitor type 1 and type 2, has been described. Because the placenta is a source of both type 1 and type 2 plasminogen activator inhibitor, we have studied them and other fibrinolytic parameters in a group of normotensive pregnant women with intrauterine fetal growth retardation and in two groups of women with preeclampsia, with or without intrauterine growth retardation. A significant increase in plasminogen activator inhibitor type 1 antigen and plasminogen activator inhibitor activity was observed in preeclampsia, with or without intrauterine growth retardation, but not in normotensive pregnancy with intrauterine growth retardation, when compared with normal pregnancy. Plasminogen activator inhibitor type 2 antigen levels showed a significant decrease in both groups of pregnant women (normotensive or preeclamptic) with intrauterine growth retardation when compared with pregnancies without intrauterine growth retardation. A significant correlation between plasminogen activator inhibitor type 2 levels and fetal weight has been observed in the clinical groups.     

Vasoconstriction of small arteries isolated from the human placental chorionic plate in normal and compromised pregnancy.

Our aim was to compare placental chorionic plate small artery function in normal pregnancies and those complicated by preeclampsia and intrauterine growth restriction. In particular we wished to test the hypothesis that the constrictive potential of placental small arteries is modified in compromised pregnancy. Biopsies were obtained from term placentas from uncomplicated pregnancies and those affected by preeclampsia and intrauterine growth restriction. Small arteries from the chorionic plate were dissected free from surrounding tissue and studied using parallel wire myography. Placental small arteries developed maintained constrictions to arginine vasopressin and the thromboxane-mimetic U46619. Arterial maximal constriction was reduced in both preeclampsia and intrauterine growth restriction. This effect was agonist independent. In intrauterine growth restriction, placental small arteries showed decreased sensitivity to U46619 but not to arginine vasopressin. Human placental chorionic plate small artery vasoconstriction is significantly reduced in compromised pregnancy, a factor that may lead to altered blood flow within the fetoplacental circulation in these conditions.     

Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia

OBJECTIVE: Maternal serum placenta growth factor levels have been shown to be significantly reduced in women with established preeclampsia. However, the temporal change in serum placenta growth factor levels before the clinical onset of preeclampsia is not known. STUDY DESIGN: Serum samples were collected from patients at the first prenatal (5-15 weeks' gestation), second-trimester (16-20 weeks' gestation), and third-trimester (26-30 weeks' gestation) visits. Serum placenta growth factor levels were determined and analyzed according to pregnancy outcome. RESULTS: Maternal placenta growth factor levels during normal gestation increased dramatically from the first to the third trimester. At the same gestational time points, in contrast, significantly lower serum placenta growth factor levels were found in patients in whom mild or severe preeclampsia eventually developed (P <.01). Low maternal serum placenta growth factor levels during early gestation were associated with a significant odds ratio for development of preeclampsia (P <.005). CONCLUSION: Relatively decreased levels of serum placenta growth factor occur before the onset of clinical preeclampsia, which suggests that placenta growth factor measurement could be used to discriminate those pregnancies predisposed to development of preeclampsia.     

Circulating angiogenic factors and placental abruption

OBJECTIVE: Abnormalities in circulating angiogenic factors have been reported in diseases of abnormal placentation, such as preeclampsia and intrauterine growth restriction. Our objective was to determine whether circulating angiogenic factors are altered in another placental vascular disease, abruptio placentae. METHODS: In a nested case-control study of nulliparous pregnancies, we examined levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in serum collected prospectively from 31 women who later developed placental abruption and from 31 normal control subjects. All serum specimens were collected before the onset of hypertension or abruption and before labor or delivery. Serum angiogenic factors were compared within 3 gestational age windows: early (20 weeks or less), middle (21-32 weeks), and late (33 weeks or more) pregnancy. RESULTS: During early pregnancy women who developed placental abruption had lower PlGF and higher sFlt-1 concentrations and higher sFlt-1/PlGF ratios than women with normal pregnancies. In mid-pregnancy these differences became greater, reaching statistical significance for PlGF concentration (431 versus 654 pg/mL, P<.01) and the sFlt-1/PlGF ratio (25.3 versus 2.5, P<.01). When the women with placental abruption were subdivided into those who did (n=10) and those who did not (n=21) develop preeclampsia or gestational hypertension, significant alterations in angiogenic factors were noted only in women who later developed hypertension in pregnancy. Among these women, PlGF concentrations were decreased in mid-pregnancy (160 versus 723 pg/mL, P<.001), and the mid-pregnancy sFlt-1/PlGF ratio was increased (70.1 versus 2.3, P=.001). CONCLUSION: Serum levels of the proangiogenic factor PlGF were decreased, and those of the antiangiogenic ratio sFlt-1/PlGF were increased in nulliparous women who subsequently developed hypertension and placental abruption.