Belmiro Patrício

Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood

Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.

Fetal and maternal angiogenic/anti-angiogenic factors in normal and preeclamptic pregnancy

Few studies evaluated angiogenic/anti-angiogenic factors and endothelial (dys)function in both maternal and umbilical cord blood (UCB) in preeclampsia (PE). We aimed to clarify the role of placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 1 (VEGFR-1) and tissue plasminogen activator (tPA), by evaluating them in maternal and UCB in 42 normal and 46 preeclamptic (PEc) cases. In PE, maternal and UCB PlGF were significantly lower; maternal VEGF, sVEGFR-1 and tPA were significantly higher. In UCB, sVEGFR-1 and tPA were significantly higher in PEc cases, while VEGF and PlGF were significantly lower. A significant correlation between maternal and UCB sVEGFR-1, and between sVEGFR-1 and tPA both in maternal and UCB, was observed in PEc cases. In maternal and UCB circulation in PE, a close interaction seems to exist between endothelial dysfunction and angiogenesis disturbance, and sVEGFR-1 seems to play a central role in those disturbances.

Fetal lipoprotein changes in pre-eclampsia

Objective. To evaluate the impact of maternal lipid changes upon the fetus in pre‐eclampsia (PE) by evaluating lipid profile simultaneously in maternal and umbilical cord blood (UCB). Design. Case‐control study performed on healthy and pre‐eclamptic pregnant women and their neonates. Setting. The Department of Obstetrics and Gynecology, Hospital S. Joao and Faculty of Pharmacy, Porto, Portugal. Samples. Forty‐two healthy pregnancies and 46 pregnancies complicated with PE. Methods. Total cholesterol (TChol), HDL‐cholesterol (HDLc), LDL‐cholesterol (LDLc) and triglycerides (TG) levels were determined using enzymatic methods. Apolipoprotein (apo) A‐I, apoB and lipoprotein (a) [Lp(a)] values were measured by immunoturbidimetry. Main outcome measures. Fetal and maternal plasma levels of TChol, HDLc, LDLc, TG, apoA‐I, apoB and Lp(a). Results. Pre‐eclamptic women presented significantly higher values for TChol, LDLc, HDLc, TG, apoA‐I and apoB compared to normal pregnant women. In the UCB from pre‐eclamptic pregnancies, we observed significantly lower values for HDLc and apoA‐I, and significantly higher TG concentrations and LDLc/HDLc ratio when compared to normal cases. A positive correlation was observed between maternal TG levels and proteinuria, a marker of PE severity (r =0.40, p <0.01). Conclusions. Our data suggest that pre‐eclamptic pregnancy is associated with an enhanced hyperlipidemia, which seems to have a negative impact on fetal lipid profile, as reflected by a higher atherogenic LDLc/HDLc ratio and higher TG levels. These children, born of women with PE, may deserve a closer clinical follow‐up later in life.

Prevalence of hypertension during pregnancy in Portugal.

Objective: To estimate the prevalence of maternal hypertensive disorders in Portugal and to assess their impact on obstetric outcomes. Methods: A national survey on hypertension in pregnancy was conducted in Portuguese public maternity wards and included 6726 pregnancies. Results: Six percent of women presented with a hypertensive disorder during pregnancy or puerperium: 1.5% with chronic hypertension, 2.5% with gestational hypertension, 1.4% with preeclampsia, 0.2% with superimposed preeclampsia, 0.1% with eclampsia, and 0.1% with HELLP syndrome. Preterm birth, small-for-gestational-age infants and fetal death were significantly more frequent among women with preeclampsia/eclampsia and HELLP syndrome. Conclusion: In Portugal, the prevalence of hypertensive disorders diagnosed during pregnancy seems to be lower than that reported in most countries, but these disorders have a significant effect on pregnancy outcomes.

Haemostatic factors in women with history of preeclampsia.

OBJECTIVE Evaluation of haemostatic parameters--Plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1) and fibrin fragment D-dimer several years after the end of pregnancy to investigate if they are modified in women with history of preeclampsia (PE). STUDY DESIGN 65 healthy women with history of PE and 54 control women with previous normal pregnancy were enrolled in this study. Groups were matched for age, time period since delivery, smoking status and alcohol consumption. t-PA, PAI-1 and fibrin fragment D-dimer antigen levels were quantified using standards commercial ELISA methods. Plasma fibrinogen was measured using automated capillary zone electrophoresis. RESULTS Systolic and diastolic blood pressures were higher in women with history of PE. Levels of t-PA, PAI-1 and fibrinogen were similar between groups as well as the t-PA/PAI-1 ratio. A significant increase in D-dimer levels was observed in women with history of PE. CONCLUSION The increase in D-dimer level suggests an abnormal haemostatic potential namely increased intravascular coagulation. This, together with the increased blood pressure, can reflect a tendency for an increased risk of cardiovascular/thrombotic events later in life.

Relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies

Endothelial cell activation or damage is believed to play a key role in preeclampsia (PE) and may underlie the hemostatic changes observed in this syndrome. The aim of this study was to evaluate a relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies. We measured the plasma levels of tissue plasminogen activator (tPA) antigen and of plasminogen activator inhibitor type 1 (PAI-1) antigen, both markers of hemostatic and endothelial function, and fibrin fragment D-dimer. Maternal blood from uncomplicated (n=42) and PEc pregnancies (n=44) were collected before delivery, and umbilical cord blood (UCB) immediately after delivery. In preeclamptic cases, UCB presented significantly higher tPA values and significantly lower PAI-1/tPA ratio. Preeclamptic women also presented significantly higher tPA, as well as PAI-1 values, when compared with normal pregnant women; no significant difference was found for D-dimer. In preeclamptic women, proteinuria (a marker of PE severity) correlated positively and significantly with tPA and PAI-1 antigen levels. An inverse relationship between maternal tPA antigen levels and fetal birth weigh in PE was also observed. Our data show that the hemostatic maternal disturbances observed in preeclamptic women have similarities with the UCB circulation, and that endothelial dysfunction is the most plausible underlying cause. Moreover, maternal hemostatic disturbances seem to be associated with the severity of PE. Further studies are needed to strength the values of tPA and PAI-1 as markers of severity in PE.

Erythrocyte changes in preeclampsia: relationship between maternal and cord blood erythrocyte damage.

Abstract Our aim was to evaluate red blood cell (RBC) changes in normal and preeclamptic cases, and to assess the relationship between maternal and umbilical cord blood (UCB) changes. We evaluated markers of RBC damage: membrane bound hemoglobin (MBH) and band 3 profile – high molecular weight aggregates (HMWSAg), monomer and proteolytic fragments. RBCs are marked for removal by a rise in MBH and in HMWAg. Preeclamptic mothers had significantly higher MBH, RBC count, hemoglobin, hematocrit, reticulocytes and reticulocyte production index (RPI). In UCB from newborns of preeclamptic mothers, we found similar HMWAg, RBC count, hemoglobin and hematocrit; significantly higher MBH, mean cell hemoglobin concentration, mean cell volume, RPI and reticulocyte count. Maternal MBH and HMWAg values were positively and significantly correlated with MBH and HMWAg values in UCB, in normal as well as in preeclamptic pregnancies; in preeclampsia, a significant positive correlation between UCB and maternal bilirubin, and between RPI and proteinuria were found. We conclude that markers of RBC damage/production are altered in preeclampsia, in both UCB and maternal circulation. Our data show similarities between UCB and maternal RBC changes, as suggested by the correlations of markers of RBC damage.