Interleukin-18 concentrations in pregnancies complicated by preeclampsia with and without IUGR: A comparison with normotensive pregnant women with isolated IUGR and healthy pregnant women

ObjectiveThe aim of present study was to assess the maternal serum levels and clinical significance of interleukin-18 (IL-18) in pregnancies complicated by preeclampsia and/or intrauterine growth restriction (IUGR).Patients and methodsThe study was carried out on 30 patients with pregnancy complicated by severe preeclampsia (15 patients with IUGR and 15 with appropriate-for-gestational-age weight fetuses), 11 normotensive pregnant patients with pregnancy complicated by isolated IUGR and 32 healthy normotensive women with uncomplicated pregnancies. The interleukin-18 levels were determined using an ELISA assay.ResultsDecreased levels of maternal serum IL-18 in preeclamptic patients with and without IUGR were observed. Contrary to the preeclamptic women, no difference was found in the maternal serum levels of IL-18 in normotensive patients with pregnancies complicated by isolated fetal growth restriction. These levels were the same as observed in the healthy controls. The mean values of maternal serum IL-18 were 219.118 ± 180.079 pg/mL in the PRE group, 438.170 ± 229.657 pg/mL in the group of women with isolated IUGR, and 457.053 ± 528.142 pg/mL in the control group. The levels of maternal serum IL-18 were similar in both study preeclamptic subgroups. The mean values of IL-18 were 204.823 ± 188.171 pg/mL in the group PI and 233.414 ± 176.995 pg/mL in the P group.ConclusionsOur findings suggest that decreased levels of IL-18 in maternal serum play a significant role in etiology and pathogenesis of preeclampsia. But normotensive pregnancies complicated by isolated IUGR are not associated with the altered interleukin 18 levels in maternal serum.     

Comparison of maternal serum levels of interleukin-10, interleukin-12, and interleukin-2 in normal and preeclamptic pregnancies

ObjectiveThe aim of this study was 2 fold: (1) to compare the maternal serum levels of IL-10, IL-12, and IL-2 in preeclamptic and normal pregnant women, and (2) to study the serum levels of these cytokines in preeclamptic pregnancies with and without intrauterine growth retardation.Study designForty women with singleton pregnancies complicated by preeclampsia (32 severe and 8 mild) and 29 normotensive healthy pregnant women were included in the study. Preeclamptic patients were further divided into 2 groups according to the presence or absence of intrauterine growth retardation. Maternal serum levels of IL-10, IL 12, and IL-2 were compared between these groups using enzyme-linked immunosorbent assays.ResultsMaternal serum levels of IL-10 were significantly higher in the preeclampsia group than in controls (p < 0.001). There were no statistically significant differences in maternal serum concentrations of IL-2 and IL-10 between the study and control groups (p > 0.05). Serum levels of IL-2 and IL-10 in the patients with preeclampsia complicated by IUGR were elevated in comparison with the uncomplicated preeclampsia group. These differences were statistically significant (p < 0.05 for both).ConclusionsIL-10 may be involved in the pathologic process of preeclampsia. Increased serum levels of IL-10 and IL-2 in preeclampsia complicated with IUGR suggests a possible role of these cytokines in IUGR.     

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.     

Higher plasma AOPP is associated with increased proteinuria excretion and decreased glomerular filtration rate in pre-eclamptic women

BackgroundAdvanced oxidation protein products (AOPP) as a novel biomarker of oxidative stress has been demonstrated in chronic kidney disease (CKD) patients. The research was to investigate the plasma AOPP level in pre-eclamptic pregnant women and its correlation with 24-h proteinuria collection, cystatin C(CC), uric acid(UA) and creatinine(Cr).MethodsFifty pre-eclamptic women, including 22 mild and 28 severe preeclampsia were enrolled. Twentyfive healthy singleton pregnant women were selected as control. Blood samples were obtained from all groups to measure the levels of AOPP, CC, UA, Cr and other biochemical parameters at admission. Total protein in the 24 h urine collection was measured. Pearson correlation was performed to evaluate the associations between plasma AOPP level and 24-h proteinuria collection, plasma cystatin C, uric acid and creatinine.ResultsThe means of AOPP levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (88.6 ± 10.0 μmmol/L, 72.1 ± 11.1 μmmol/L and 48.7 ± 11.3 μmmol/L). The means of cystatin C levels were significantly different among severe, mild pre-eclampsia and normotensive pregnant women (1.8 ± 0.6 μmmol/L, 1.2 ± 0.3 μmmol/L and 1.0 ± 0.2 μmmol/L). Mild, severe pre-eclampsia and control groups did not differ significantly from each other with respect to uric acid and creatinine. Significant positive correlation between AOPP and 24-h proteinuria excretion in preeclamptic pregnant women was found in mild and severe preeclamptic pregnant women (r = 0.792). Significant positive correlation between AOPP and cystatin C was found in normal and preeclamptic pregnant women (r = 0.521).ConclusionPlasma AOPP level had a significant positive correlation with 24-h proteinuria excretion and cystatin C. Further research about the relevance between the level of AOPP and the onset of preeclampsia was needed in order to have a profound prospective in oxidative stress and preeclampsia.     

Serum S100B in pregnancy complicated by preeclampsia: A case-control study

BackgroundSerum S100B is a protein produced and released primarily by astrocytes of the Central Nervous System (CNS). Elevated levels of serum S100B are associated with several types of pathological conditions of the brain, including the eclampsia in pregnant women. The aim of this study was to compare serum S100B concentrations in pregnant women with severe and mild preeclampsia (PE) with S100B serum levels in normotensive pregnant women.Material and methodsSerum S100B protein was measured in normotensive pregnant women (n = 15) and in women with mild PE (n = 12) or severe PE (n = 34). The serum S100B level (μg/L) was determined by an luminometric assay.ResultsSixty-one expectant mothers were studied, aged 26.6 ± 8.7 (mean ± SD) years and with a gestational age of 33.3 ± 4.2 weeks. The severe PE group demonstrated higher S100B levels (0.20 ± 0.19), as compared with mild PE (0.07 ± 0.05) or normotensive groups (0.04 ± 0.05).ConclusionElevated serum S100B levels in pregnant women with severe PE suggest that some kind of neural damage and subsequent astrocytic release of S100B is not dependent on the progression from severe preeclampsia to eclampsia.     

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.     

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.     

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.     

Placental Release of Distinct DNA-associated Micro-particles into Maternal Circulation: Reflective of Gestation Time and Preeclampsia

BackgroundThe aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia.MethodsDNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis.ResultsDNA-associated HLA-G⁺ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in the first and second trimesters. DNA-associated PLAP⁺ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in the second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G⁺ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G⁺ MPs from the plasma of normal pregnant women (p < 0.03).ConclusionsHLA-G⁺ and PLAP⁺ MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G⁺ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts.     

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.     

Intérêt du dosage des d-dimères comme marqueurs de sévérité en cas de prééclampsie

ObjectivesAlterations in blood coagulation and fibrinolysis play a major role in the pathogenesis of preeclampsia. HELLP syndrome is associated with hypercoagulability and leads to maternal and perinatal complications. Our purpose was to evaluate d-dimer as a marker for severity in pregnancies with preeclampsia.Patients and methodsPlasma d-dimer levels were measured using an enzyme-linked immunosorbent assay (ELISA) technique. We studied the association between d-dimer levels and clinical and biological characteristics of pregnancies complicated by preeclampsia.Resultsd-dimer values increased with increasing gestational age. Patients with HELLP syndrome had mean d-dimer values significantly greater than patients with preeclampsia alone (3848 ± 2551 versus 1578 ± 1077, P < 0.001). However, the level of d-dimer at the time of admission was poorly predictive of occurrence of HELLP syndrome. Area under of the ROC curve was 0.69 (CI 95%: 0,59–0,79). The best threshold was 2170 ng/mL with a sensitivity of 0.91 and a specificity of 0.40. Other severity criteria of preeclampsia were not associated with higher levels of d-dimer.Discussion and conclusionIn preeclamptic patients, d-dimer levels were related with gestational age and HELLP syndrome. However, accuracy of this test to predict occurrence of HELLP syndrome or severe preeclampsia was too low to recommend its use routinely.     

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study

ObjectiveTo determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction.MethodsThis is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5 months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45 years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration.ResultsSixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p < 0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR = 6.18, 95% CI 1.59, 24.02; p = 0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction.ConclusionsOur study supports previous findings that preeclampsia is associated with diastolic dysfunction.     

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.     

Maternal serum ratio of ghrelin to obestatin decreased in preeclampsia

ObjectiveGhrelin, an endogenous for the growth hormone secretagogue receptor, has been shown to participate in blood pressure regulation. Obestatin, encoded by the same gene as ghrelin, is described as a physiological opponent of ghrelin. We hypothesized that ghrelin/obestatin imbalance played a role in the pathogenesis. This study was designed to determine the alterations of ghrelin and obestatin concentrations and ghrelin/obestatin ratio in maternal serum in preeclampsia.MethodThis retrospective case–control study included 31 preeclampsia and 31 gestational week-matched normal pregnancies. Ghrelin and obestatin concentrations in maternal serum were determined by radioimmunoassay, and the ghrelin/obestatin ratio was calculated.ResultsThe ghrelin concentration and ghrelin/obestatin ratio in maternal serum were significantly lower in preeclampsia than in normal pregnancies (214.34 ± 14.27 pg/mL vs 251.49 ± 16.15 pg/mL, P = 0.041, 1.07 ± 0.09 vs 0.82 ± 0.08, P = 0.023). The obestatin concentration in maternal serum was significantly higher in preeclampsia than in normal pregnancies (276.35 ± 15.38 pg/mL vs 223.53 ± 18.61 pg/mL, P = 0.019). The systolic blood pressure in preeclampsia was negatively correlated with ghrelin concentration and ghrelin/obestatin ratio (r = −0.549, P = 0.003; r = −0.491, P = 0.004) and was positively correlated with obestatin concentrations in preeclampsia (r = 0.388, P = 0.013).ConclusionsThe findings of this study suggested disturbance of ghrelin and obestatin in maternal serum in preeclampsia, and ghrelin/obestatin imbalance might play a role in the pathogenesis of preeclampsia.     

Transfer function analysis of dynamic cerebral autoregulation in preeclampsia

ObjectiveThe cerebral circulatory effects of preeclampsia on the latency (phase) and the efficiency (gain) of the cerebral autoregulatory response is unknown. Preeclampsia causes a progressive impairment of the cerebral autoregulatory response. We sought to identify these dynamic cerebral autoregulation changes in preeclampsia.Study designWe simultaneously measured continuously beat to beat outputs of mean arterial pressure (MAP) (Pilot 9200) and beat to beat, systolic, diastolic, and mean cerebral blood flow (MCBFV) (Nicolet Vascular TCD) for 2 min with the patient during supine rest. Five preeclamptic and 5 matched normotensive controls were studied. R–R intervals, MAP, and MCBFV were analyzed in the frequency domain. Data sets were fast Fourier transformed and power spectral densities were calculated. We calculated the phase angle (which represents the temporal relationship between the MAP and mean MCBFV) and the transfer function (amplitude or gain between changes in the MCBFV signal and the MAP signal). All continuous data was compared between the two groups using T tests.ResultsWe identified a significant difference between (1) the gain between the normotensive and preeclamptic groups (.29 ± .07 vs .10 ± .04) (p < .01, and (2) the phase angle (59 ± 12 vs 129 ± 31), p < .01. The preeclamptic group showed significant decrease in gain but an increase in phase angle).ConclusionPreeclampsia paradoxically results in a significant improvement in dynamic cerebral autoregulation as demonstrated by an increase in phase and a decrease in gain. Clinical studies that can systematically assess the progression of these dynamic autoregulation changes are needed.     

Cardiovascular risk markers in pregnancies complicated by diabetes mellitus or preeclampsia

ObjectiveTo explore biomarkers indicating cardiovascular disease in pregnant women with diabetes or preeclampsia, since these women are at increased risk for future cardiovascular disease.Study designEDTA-plasma from 262 women in gestational week 24–42 (healthy pregnancies n = 71, preeclampsia n = 105, type 2 diabetes n = 17, gestational diabetes n = 61, diabetes with preeclampsia n = 8) was analyzed by immunoassay for neopterin, midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-arginine vasopressin (CT-proAVP). The diabetes groups were also analyzed for midregional pro-atrial natriuretic peptide (MR-proANP), and compared to previously reported MR-proANP concentrations for healthy, normotensive and preeclamptic patients.ResultsIn contrast to preeclampsia, median plasma MR-proANP was not increased in pregnancies complicated by diabetes, but in fact lower, compared to healthy pregnancies. Neopterin was increased in diabetic pregnancies and in late onset preeclampsia, compared to healthy pregnancies. Median plasma MR-proADM was increased in pregnancies complicated by gestational diabetes or preeclampsia, compared to healthy pregnancies. Median plasma MR-proANP was increased in diabetic pregnancies complicated by preeclampsia compared to pregnant women with diabetes only.ConclusionWomen with pregnancies complicated by diabetes mellitus or preeclampsia are at risk for future cardiovascular disease, but differ in circulating cardiovascular biomarker profile. A cardiovascular biomarker profiling during pregnancy might prove helpful in identifying women at risk for future cardiovascular disease, thus enabling targeted prophylactic interventions and follow-up.     

Maternal and Umbilical sTNF-R1 in Preeclamptic Pregnancies with Intrauterine Normal and Growth Retarded Fetus

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFα and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.     

Endothelial nitric oxide synthase (eNOS) gene Glu298Asp polymorphism and expression in North Indian preeclamptic women

BackgroundPathophysiological processes in preeclampsia (PE) are influenced by genetic factors, nitric oxide synthases seem to play important roles, although their expression in and their role is still unclear. To better characterize the host genetic factors determining the susceptibility to PE, we evaluated the influence of polymorphisms (Glu298Asp) in the endothelial nitric oxide synthase (eNOS) gene on the risk of developing PE by checking the expression level.MethodsWe conducted a hospital-based case-control study including 300 women with preeclampsia and 200 healthy pregnant women. Their blood samples were analyzed for levels of nitric oxide, eNOS gene polymorphism and expression. eNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction with control β-Actin gene mRNA levels.ResultsThe mRNA expression of eNOS gene was found to be significantly lower in blood (P < 0.05) from women with PE compared to that from normal pregnancies. The total nitric oxide levels (P < 0.001) were decreased in study Group as compared to healthy pregnant patients. The intergenotypic variation of nitric oxide levels in preeclamptic women was found to be significant (P < 0.001).ConclusionsThese results indicate the relationship between reduced nitric oxide levels and eNOS gene polymorphism leading to its altered expression in preeclamptic women.     

Abnormal uterine artery Doppler velocimetry predicts adverse outcomes in patients with abnormal analytes

ObjectivesOur aim was to determine if uterine artery (UtA) Doppler studies would risk-stratify women with abnormal serum analytes on prenatal genetic screening into those at baseline and increased risk for preeclampsia and small-for-gestational age (SGA).Study designThis retrospective cohort study examined outcomes of patients with ⩾one abnormal analyte (PAPP-A < 0.3, hCG > 3.0, AFP > 2.5, inhibin > 2.0, or unconjugated estriol < 0.3MoM). At approximately 24 weeks, we assessed UtA pulsatility index (PI).Main outcome measuresPreeclampsia, preterm preeclampsia, SGA (birthweight (BW) <10%) and intrauterine growth restriction (IUGR) (BW < 3%).ResultsWe identified 132 patients with ⩾one abnormal analyte, UtA Doppler screening, and delivery outcomes. Twenty-four (18%) had an elevated UtA PI (PI > 1.6); preeclampsia occurred in 16 (12%) and 26 (20%) delivered a SGA neonate. Abnormal UtA Doppler PI increased the likelihood of a composite outcome of preeclampsia or SGA from 27% to 71% (LR 6.48 (2.93, 14.30)); a negative UtA Doppler PI reduced the likelihood to 18% (LR 0.57 (0.42, 0.78)). Abnormal UtA Doppler PI increased the likelihood of a more severe composite outcome of preterm preeclampsia or IUGR from 11% to 39% (LR 5.49 (3.03, 9.97)); a negative UtA Doppler study reduced the likelihood to 4% (LR 0.35 (0.16, 0.80)).ConclusionsIn patients with abnormal serum analytes, abnormal UtA Doppler PI is significantly associated with preeclampsia or SGA and improves the prediction of these adverse outcomes by 9–15-fold. Providers can incorporate UtA Doppler PI into an abbreviated surveillance regimen; they can be reassured that a normal study markedly decreases the risk of a severe early adverse outcome.     

Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine normal and growth retarded fetus.

OBJECTIVE: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS AND CONCLUSIONS: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.