Apolipoprotein E Genotypes,Lipid Peroxidation,and Antioxidant Status among Mild and Severe Preeclamptic Women from Western Iran: Protective Role of Apolipoprotein ϵ2 Allele in Severe Preeclampsia

Objective. The aim of this study was to examine the association of apolipoprotein E (APOE) genotypes and oxidative stress with the risk of mild and severe preeclampsia. Methods. In a case–control study, 198 women with preeclampsia including 128 women with mild and 70 women with severe preeclampsia and 101 control pregnant women from Western Iran were studied. The APOE genotypes were identified using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. The serum level of malondialdehyde (MDA) and total antioxidant capacity (TAC) were determined using high-performance liquid chromatography and commercial kits, respectively. Results. The frequency of APOE ?2 allele in severe preeclamptic women (2.1%) was significantly (p = 0.008) lower than that in controls (9.4%). The presence of APOE ?2 allele was associated with around five times decreased risk of severe preeclampsia [OR = 0.21 (95% CI = 0.6–0.73, p = 0.014)]. A significantly higher serum level of MDA was observed in women with severe (10.87 ± 4.61 μM) and mild (9.81 ± 3.67 μM) preeclampsia compared with that in controls. A trend toward decrease serum level of MDA was observed according to the APOE alleles as ?2 < ?3 < ?4 (9.23, 10.22, and 10.43 μM, respectively). In preeclamptic women, an inverse correlation was detected between serum levels of MDA and HDL-C (r = ?0.16, p = 0.029). However, there was a direct correlation between serum level of MDA with diastolic blood pressure (r = 0.15, p = 0.037). Conclusion. Our study in a population with Kurdish ethnic background indicates a protective role for APOE ?2 allele against severe preeclampsia that might be through high antioxidant capacity of this allele.     

Oxidative stress and immunological alteration in women with preeclampsia

Objectives: To determine plasma concentrations of malondialdehyde (MDA) and of inflammatory markers in women with preeclampsia. Methods: A case–control study was conducted on 50 preeclamptic and 50 healthy pregnant women. The concentrations of MDA were determined by the method of thiobarbituric acid reactive substances. Markers of inflammation were determined by the multiplex method. Results: The concentrations of MDA did not differ between groups (p?>?0.05) and the preeclampsia group had significantly higher IL-6, IL-10, TNF-α and IL-6/IL-10 ratio, compared to those with normal pregnancy. Conclusions: The MDA is a nonspecific marker for oxidative stress in preeclampsia, and the gestantes with preeclampsia have immune dysfunction.     

Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO25% inhalation in preeclamptic women

Abstract

Objective: To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2_5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia.

Study design: A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2_5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded.

Results: Baseline PI and RI were lower in the preeclamptic group (p?<?0.05). Inhalation of CO2_5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006?±?0.229 versus 0.503?±?0.209, p?=?0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583?±?0.193 versus 0.383?±?0.173, p?=?0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve?=?0.973, p?=?0.0001).

Conclusion: CVR in response to CO2_5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.     

SERUM ANTIBODIES TO OXIDIZED LOW-DENSITY LIPOPROTEIN IN PREGNANT WOMEN WITH PREECLAMPSIA AND CHRONIC HYPERTENSION: LACK OF CORRELATION WITH LIPID PEROXIDES

Objectives: To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension.

Methods: Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension.

Results: Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women.

Conclusions: Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels.     

The relation of maternal serum eNOS,NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction

Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels 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.

Patients and methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure >?160/110?mmHg with proteinuria >?5?g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays.

Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed.

Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.     

Urinary clusterin and glutathione-s-transferase levels in HIV positive normotensive and preeclamptic pregnancies

Objective: To determine the level and effect of urinary clusterin (CLU) and glutathione-s-transferase (GST) proteins in normotensive and preeclamptic pregnant women with HIV infection. Methods: The urine concentration of CLU and GST in normotensive (n = 38) and preeclamptic pregnant (n = 38) women stratified by HIV status were estimated using the Bio-Plex® Pro^TM immunoassay. Results: Across the group, a significant down-regulation of CLU (p = 0.039) with a reduced trend in GST was shown in HIV positive preeclampsia. Conclusion: HIV infection affects the activity of urinary CLU protein in HIV positive preeclampsia. However, the cytoprotective role of these proteins neutralizes the oxidative radicals associated with preeclampsia development through complement response in HIV infection.     

Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia.

AIMS: To evaluate changes in lipid profile, serum levels of malondialdehyde (MDA) and lipoprotein(a) (Lp(a)) and placental MDA in preeclamptic women, and to evaluate the atherogenic role of these changes in the pathophysiology of pre-eclampsia. METHOD: A cross-sectional study was performed in 20 normal pregnant women, 25 women with mild preeclampsia and 28 women with severe preeclampsia in the third trimester. MDA, which is the endproduct of lipid peroxidation, was measured in placental tissue by the thiobarbituric acid (TBA) method of Ohkawa and colleagues and in serum by the TBA method of Asakawa and Matsushita. Serum lipid levels were measured by with an autoanalyzer, serum apolipoprotein (Apo) A-I and Apo B were measured by nephelometric assay and serum Lp(a) level using a nephelometric agglutination assay method. In preeclamptic and normal pregnant women, multiple comparisons between groups were performed by one-way analysis of variance supplemented with Tukey's HSD post hoc test. The association between placental and serum concentrations among groups was analyzed using the Pearson correlation test. RESULTS: Serum levels of MDA, Lp(a), total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and placental MDA were significantly higher, and high-density lipoprotein cholesterol (HDL-C) and Apo A-I levels were significantly lower, in severely preeclamptic and mildly preeclamptic women than in the normal pregnant women, but no difference was observed in Apo B among groups. Serum level of Lp(a) was positively correlated with body mass index in severely preeclamptic women (r=0.489, p=0.008). A significant positive correlation was also found between serum level of MDA and systolic blood pressure in women with severe preeclampsia (r=0.375, p=0.049). CONCLUSIONS: Our findings suggest that high Lp(a), lipid peroxidation, LDL-C and TG, and low HDL-C and Apo A-I levels, are important risk factors for atherosclerosis among preeclamptic women.     

Maternal serum autotaxin levels in early- and late-onset preeclampsia

Purpose: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital.

Methods: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients.

Results: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels.

Conclusion: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.     

Distribution of apolipoprotein(a) isoforms in normotensive and severe preeclamptic women

Objective: Preeclampsia is a pregnancy-related disorder constituting one of the primary causes of worldwide maternal and fetal mortality, but despite intensive research its pathogenesis remains unclear. Lipids have been implicated in the development of preeclampsia, although this possible association remains controversial and not yet fully investigated. This study set out to examine the potential association between lipoprotein(a) and the development of severe preeclampsia. The focus of this study was to investigate the potential utility of apolipoprotein(a) isoforms as possible diagnostic markers for identifying women at risk for developing preeclampsia.

Methods: Study participants included a control group of nonpregnant female volunteers (n = 59), a group of healthy pregnant (normotensive) female volunteers (n = 51), and a group of severe preeclamptic female volunteers (n = 59). Serum lipoprotein(a) concentrations were measured using double-antibody ELISA methods and were found to be 17.0 ± 23.6 mg/dl among nonpregnant controls (n = 51), 15.9 ± 15.8 mg/dl among healthy pregnant normotensives (n = 51), and 16.2 ± 16.7 mg/dl in the preeclamptic group (n = 59). In addition, apolipoprotein (a) isoforms were identified using high-resolution SDS-agarose electrophoresis followed by immunoblotting.

Results: We detected no significant differences between the groups studied in the distribution of isoforms (Chi-square = 1.21, df = 4, P = 0.89); however, in a 1-week interval we detected a 42.2% rise in Lp(a) levels as well as a 67.1% rise in C-reactive protein concentrations among 10 volunteers in the preeclamptic group (median = 9.6; P < 0.05).

Conclusions: Although the exact mechanism of pathogenesis continues to elude investigators, our results suggest that lipoprotein(a) may act as an acute-phase reactant during preeclampsia. Although our results are preliminary, they are consistent with growing evidence implicating lipids as among those factors involved in the etiology of preeclampsia. Changes in apoliprotein(a) may be among those important biochemical markers that are found to be useful in the early identification of high-risk women and warrant further study.     

Ischemia-modified albumin as an oxidative stress marker in preeclampsia

Objective.?We examined serum ischaemia-modified albumin (IMA) levels in normal pregnant and preeclamptic women. The primary aim of our study was to assess IMA in women with mild and severe preeclampsia.

Methods.?Serum ischaemia-modified albumin levels were measured in 18 normotensive and 36 preeclamptic pregnant women by enzyme linked immuno-sorbent assay. Patients were subdivided as having either mild (n?=?18) or severe preeclampsia (n?=?18). Receiver operating characteristic curve was constructed, and sensitivity and specificity were calculated based on the best cut-off.

Results.?IMA levels were significantly higher in the mild and severe preeclamptic groups than in the control group. IMA with a cut-off point of 0.31 identified women with preeclampsia with sensitivity 80% and specificity 77.8%.

Conclusion.?Our study demonstrates that serum levels of IMA correlate with severity of preeclampsia.     

Plasma Factors that Determine Endothelial Cell Lipid Toxicity in Vitro Correctly Identify Women with Preeclampsia in Early and Late Pregnancy

Objective: We proposed that women who develop preeclampsia have a low ratio of “protective” toxicity preventing activity (TxPA) to “toxic” very low density lipoproteins (VLDL) late in pregnancy. Having confirmed this hypothesis, we then tested whether this low ratio would manifest itself early in the pregnancy of women who develop preeclampsia.

Methods: Serially collected plasma from women who developed preeclampsia and from matched controls was assayed blind for TxPA, tri-glycerides, cholesterol, high-density lipoproteins, albumin, and nonesterified fatty acids (NEFA).

Main Outcome Measures: Plasma concentrations of lipids, NEFA, and proteins which bind NEFA (TxPA and albumin) were measured in normal and preeclamptic women. These parameters were formulated prior to data collection because of the low albumin/triglyceride ratios and the elevated NEFA levels reported to occur in preeclampsia.

Results: In late pregnancy, TxPA was lower (1.82 ± 0.63 vs. 2.30 ± 0.40 g/dL, P = 0.008) and VLDL higher (292 ± 130 vs. 206 ± 60 mg/dL, P = 0.013) in preeclamptics than in controls. Discrimination analysis (TxPA and triglyceride), correctly classified 95% of the preeclamptics and 79% of the controls in late pregnancy. The ratio of TxPA to non-TxPA and triglyceride correctly classified 92% of the preeclamptics and 85% of the controls in early pregnancy.

Conclusions: The ratio of TxPA to VLDL accurately distinguishes preeclamptic from normal pregnant women, suggesting that both these factors are involved in the development of preeclampsia.     

Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women

Objective: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women.

Methods: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system.

Results: The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preeclamptic women compared with controls {p?=?0.04, odds ratio (OR) [95% class interval (CI)]?=?1.6 (1.0–2.5)}. The prevalence of the CT genotype [p?=?0.01, OR (95% CI)?=?1.8 (1.1–2.8)] and the dominant model (CT?+?TT) [p?=?0.03, OR (95% CI)?=?1.6 (1.1–2.5)] of the IL1A rs1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p?=?0.04, OR (95% CI)?=?0.6 (0.4–0.9)] and the dominant model (GA?+?AA) [p?=?0.03, OR (95% CI)?=?0.6 (0.4–0.9)] of the MBL1 rs1800450 polymorphism were reduced in preeclamptic women compared to controls.

Conclusion: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women.     

Increased oxidant generation in the metabolism of hypoxanthine to uric acid and endothelial dysfunction in early-onset and late-onset preeclamptic women

Objective: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. Methods: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. Results: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. Conclusions: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.     

HSP70 Overexpression in Response to Ureaplasma urealyticum–Mediated Oxidative Stress In Preeclamptic Placenta

Objective. To determine the effect of Ureaplasma urealyticum infection on oxidative stress during preeclampsia. Methods. The relationship between oxidative stress and U. urealyticum infection was monitored through the estimation of lipid hydroperoxidation level (LHP), glutathione redox ratio (GRR), and total antioxidant capacity (TAC) along with heat shock protein 70 (HSP70) expression in the placenta. Microbial growth analysis was used for U. urealyticum detection. Results. U. urealyticum infection was found in 43.7% of the preeclamptic subjects. The increased LHP level (p < 0.05) along with decreased GRR (p < 0.05) and TAC (p < 0.05) was noted in preeclamptic patients with U. urealyticum infection compared with uninfected preeclamptic and normal subjects. Under such condition, an increase in the HSP70 levels in the infected preeclamptic samples by 24.6% (p < 0.05) on comparison with uninfected preeclamptic samples was observed. Conclusion. Overexpression of HSP70 in the placental homogenate suggests the contribution of infection to oxidative stress development and the possible protective role of HSP70 against infection.     

Maternal/newborn VEGF-C936T interaction and its influence on the risk,severity and prognosis of preeclampsia,as well as on the maternal angiogenic profile

Abstract

Objective: To analyze the influence of maternal/newborn vascular endothelial growth factor (VEGF)-CT936 interaction as a modulating factor in preeclampsia as well as its influence on the maternal angiogenic balance.

Methods: Seventy pairs of preeclamptic women/newborns and 94 pairs of normal pregnant mothers/newborns were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum VEGF and soluble VEGF receptor-1 (sVEGFR-1) levels were measured using ELISA.

Results: The risk to develop mild (odds ratio; OR: 3.79, p?=?0.008) and severe (OR: 2.94, p?=?0.037) preeclampsia being increased in association with the CT936-VEGF genotype and increased in severe preeclampsia to 6.07 (p?=?0.03) if the women were carriers of the homozygous TT936-VEGF genotype. The presence of the VEGF-T936 allele in both the mother and the newborn significantly increases the risk of pregnancy-induced hypertension (PIH), mild and severe preeclampsia. If both the mothers and newborns were carriers of the VEGF-T936 allele, significantly lower VEGF and higher sVEGFR-1 levels were observed for all types of preeclampsia. Pregnant women with PIH and severe preeclampsia delivered at a significantly earlier gestational age neonates with a significantly lower birth weight if both the preeclamptic mothers and their newborns were carriers of the VEGF-T936 allele.

Conclusions: Our study suggests the role of maternal/fetal VEGF-CT936 polymorphism as a modulating factor in preeclampsia, which affects the angiogenic balance in preeclamptic mothers, as well as their pregnancy outcome.     

Newborn LpL (Ser447Stop,Asn291Ser) genotypes and the interaction with maternal genotypes influence the risk for different types of preeclampsia: modulating effect on lipid profile and pregnancy outcome

Aim: To establish that newborn Ser447Stop and Asn291Ser may have interactive effects with maternal genotypes on the plasma lipoprotein levels, risk of preeclampsia as well as on the prognosis of preeclampsia.

Materials and methods: Seventy preeclamptic women and 94 normotensive pregnant women, and their newborns were genotyped using PCR-RFLP methods.

Results: The risk of mild and severe preeclampsia was 4 (p?=?0.004) and 5.18 (p?=?0.001), respectively, if both the mother and newborn were carriers of the Ser447/Ser477 genotype. If both the mother and newborn were carriers of the Asn291Ser variant, the risk to develop severe preeclampsia was 6.07 (p?=?0.03). Women with mild and severe preeclampsia had higher TG (p?p?p?=?0.008; p?Ser447/Ser447 genotype. Women with severe preeclampsia had significantly higher TG (p?=?0.03) and LDL-C levels (p?=?0.037) if both the mother and newborn were carriers of Asn291Ser. Newborn/maternal LpL interaction had no statistically significant influence on pregnancy outcome.

Conclusions: The newborn/maternal LpL interaction influences the severity of preeclampsia and modulates the lipid profile particularly in severe preeclampsia.     

Atherogenic profile in preeclampsia

Atherosis is accepted to underlie the pathogenesis of preeclampsia, therefore we aimed to determine malonyldialdehyde (MDA) levels as a marker of lipid peroxidation, and lipoprotein(a) (Lp(a)), apolipoprotein A-1 (Apo A-1) and apolipoprotein B (Apo B) levels as a marker of atherogenic profile in preeclamptic and normal pregnant women. Twenty preeclamptic and 20 gestational-age matched normal pregnant patients were enrolled in the study, mean gestational ages for the preeclamptic and the control group were 33.9+/-1.4 and 35.5+/-0.7 weeks, respectively. Blood was withdrawn from the patients soon after diagnosis, and from the controls at their routine prenatal visits. MDA levels was significantly higher in preeclamptic patients (P=0.0003), but no difference was observed in Apo A-1 and Apo B and Lp(a) levels between the 2 groups. We consider that higher MDA was due to oxidative stress seen in preeclampsia, and similar Apo A-1 and Apo B and Lp(a) levels were due to lack of systemic atherosis.     

Plasma Hemopexin Activity in Pregnancy and Preeclampsia

Objective: Plasma hemopexin activity, associated with increased vascular permeability, was evaluated in healthy pregnant and non-pregnant women and in pre-eclamptic women. Methods: Hemopexin activity and the hemopexin inhibitor, extracellular ATP, were assayed in plasma from pregnant (n?=?10), preeclamptic (n?=?9), and non-pregnant women (n?=?10) using standard methods. Abdominal fascia tissue fragments from preeclamptic and pregnant women were immunohistochemically stained for vascular ecto-apyrase or ecto-5′nucleotidase. Results: The data show significantly enhanced Hx activity exclusively in plasma from pregnant women and significantly enhanced plasma ATP in pre-eclamptic women compared with the other groups. Dephosphorylation of preeclamptic plasma resulted in reactivation of Hx activity. Fascia tissue-samples from preeclamptic women showed reduced ecto-apyrase activity and enhanced ecto-5′nucleotidase activity compared to pregnant women. Conclusion: Enhanced hemopexin activity may be associated with normal pregnancy, but not with preeclampsia. Decreased hemopexin in pre-eclamptic patients may be due to enhanced plasma ATP, which is possibly promoted by diminished activity of vascular ecto-apyrase.     

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.