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Objectives: To clarify the changes in serum C-reactive protein (CRP) levels and in the neutrophil activation state during normal human pregnancy., Materials and Methods: A longitudinal study (n=23) was performed during the three trimesters of pregnancy; a group of non-pregnant women (n=24) was used as control. Total and differential leukocyte count, serum concentration of CRP and plasma levels of granulocyte-macrophage colony stimulating factor (GM-CSF) and of lactoferrin and elastase (two indirect markers of neutrophil activation) were measured., Results: Pregnancy imposed an inflammatory response in the mother, observed by the significant increment in total white blood cell (WBC) and neutrophil counts and in the circulating levels of CRP, GM-CSF and lactoferrin, in all trimesters of gestation compared with non-pregnant controls. Plasma elastase concentration was also significantly higher in pregnant women, but only in the first trimester of gestation. Regarding the ratios of lactoferrin and elastase per neutrophil, they were significantly lower in pregnant women (all trimesters). During gestation, WBC and neutrophil count increased significantly from the first to the second trimester and remained high in the third period. In contrast, the ratios of lactoferrin and elastase per neutrophil decreased significantly from the first to the second trimester, remaining low in the last trimester. Concerning CRP levels, no consistent changes were observed throughout gestation; 12 cases (52.2%) presented fluctuations, whereas 7 (30.4%) showed progressive reductions and 4 (17.4%) progressive increments throughout pregnancy., Conclusions: Changes in CRP levels vary in a wide manner between subjects along pregnancy, even though median values are consistently elevated throughout pregnancy. Moreover, circulating levels of neutrophil-activation products are higher in normal human gestation.

The aim of our work was to evaluate changes in levels of oxidised low-density lipoprotein (Ox-LDL) during pregnancy and how they correlate with changes in LDL size and serum total antioxidant status (TAS). LDL peak and mean particle diameter (LDL-PPD and LDL-MPD, respectively) and the relative proportion of 3 LDL subfractions were quantified. We evaluated plasma levels of Ox-LDL and serum levels of TAS, total cholesterol (Chol), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), HDL-cholesterol (HDLc) and LDL-cholesterol (LDLc). A longitudinal study was performed in the three trimesters (T1-T3) of pregnancy in normal pregnant women (n = 23) and a non-pregnant group (n = 18) was used as control. TG levels were significantly elevated whereas LDL-MPD and LDL-PPD were significantly reduced in T1 compared to controls. Ox-LDL, TG, Chol, apo B and LDLc rose markedly throughout pregnancy with significant changes between each trimester; LDL-PPD, LDL-MPD and TAS levels decreased significantly from T1 to T3. Changes in LDL size and in Ox-LDL and TAS levels were more pronounced between T1 and T2 than between T2 and T3. HDLc and apo A-I reached peak concentration in T2 but decreased in T3. TG concentrations correlated inversely with LDL size and positively with Ox-LDL; Ox-LDL was positively and strongly correlated with LDLc. Moreover, relative changes in the levels of Ox-LDL correlated inversely with relative changes in LDL size and TAS between trimesters. In conclusion, during human gestation the change in LDL profile towards smaller species and the decrease in serum TAS are closely associated with increased levels of Ox-LDL. The exact physiological role of the increments in Ox-LDL during pregnancy remains to be clarified.

The aim of this study was to evaluate changes in lipids, apolipoproteins and lipoproteins in Portuguese pregnant women and their potential involvement in the pathophysiology of preeclampsia. A cross-sectional study was performed by collecting blood samples in the first (n=64), second (n=48) and third (n=67) trimesters and puerperium (n=32) of normal pregnancies. Samples from preeclamptic women were obtained in the third trimester (n=51) and in puerperium (n=26). As normal pregnancy progressed and triglyceride (TG) levels rose there was a decrease in low density lipoprotein (LDL) size, as measured by peak and mean particle diameter (MPD), with an increased proportion of atherogenic small dense LDL. Preeclamptic women exhibited, in the third trimester and puerperium, higher mean serum TG concentration and lower high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) levels compared with healthy pregnant women. In the third trimester, LDL-mean particle diameter (LDL-MPD) and LDL cholesterol-apolipoprotein B (LDLc-apo B) ratio were also significantly reduced in the pathologic group. We conclude that human gestation is associated with an 'atherogenic' lipid profile that is further enhanced in preeclampsia and that this profile may be a potential contributor to endothelial cell dysfunction.

The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur. [ABSTRACT FROM AUTHOR]

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process. We measured total and differential leukocyte count, serum C-reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross-sectional study was performed by evaluating healthy and pre-eclamptic women in the third trimester of gestation (n = 6 7 and n = 51, respectively) and 24 to 48 h postpartum (n = 3 2 and n = 26, respectively). When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM-CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group. In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy.Materials and Methods: A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis.Results: No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two.Conclusions: Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women. [ABSTRACT FROM AUTHOR]