Relation Between Maternal Angiogenic Factors and Utero-Placental Resistance in Normal First- and Second-Trimester Pregnancies

Objective. Soluble endoglin (sEng) is a novel antiangiogenic protein and elevated sEng concentrations in maternal circulation are closely related to preeclampsia and HELLP syndrome. As the perfusion of the uterine arteries as well as the dynamics of angiogenic factors between first and second trimester have prognostic value regarding pregnancy outcome, it was the aim of this study to investigate the relation between maternal angiogenic factors and uterine Doppler parameters. Study design. The longitudinal study includes 50 normal pregnancies. Pulsatility index (PI) of the uterine arteries was detected by Doppler ultrasound in first and second trimester. In parallel, maternal sEng and soluble fms-like tyrosine kinase 1 (sFlt1) concentration was measured using ELISA. Results. In the first trimester, the sEng concentrations were 4.92 ± 1.36 ng/mL and the uterine PI was 1.14 ± 0.28. In the second trimester, the maternal sEng concentration decreased significantly to 3.99 ± 0.63 ng/mL (p < 0.05) which was associated by a decrease of the uterine PI to 0.78 ± 0.15 (p < 0.001). Soluble fms-like tyrosine kinase 1 concentrations did not differ significantly between first and second trimester (423 ± 333 vs. 444 ± 291 pg/mL). There was a significant negative correlation between sEng and uterine resistance in the second trimester (r = ?0.416; p < 0.001). Conclusions. In normal pregnancy, parallel to the fall of utero-placental resistance, there is a physiological decline of the maternal sEng concentration between first and second trimester. In second trimester, there is a negative correlation between sEng and uterine Doppler parameters.     

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.     

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.     

Changes in Maternal Serum Thioredoxin (TRX) Levels after Delivery in Preeclamptic and Normotensive Pregnant Women

Objective. To investigate changes of maternal plasma thioredoxin (TRX) levels after delivery in preeclamptic and normotensive pregnant women. Methods. Ten normotensive women (group A) were compared to 17 women with severe preeclampsia (group B). TRX levels were assessed in maternal plasma, immediately after delivery and 12–16 weeks postpartum. Results. There were no differences in plasma TRX levels between the two groups immediately antepartum (p = 0.095). A significant reduction in plasma TRX levels was found immediately following delivery only in normotensive group (117.76 ± 37.19 ng/mL vs. 43.45 ± 21.11 ng/mL, p = 0.002), but not in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 53.82 ± 44.34 ng/mL, p = 0.12). Plasma TRX levels remained unchanged in women with preeclampsia (80.42 ± 59.95 ng/mL vs. 55.37 ± 52.23 ng/mL, p = 0.2) at 12–14 weeks postpartum.     

Decreased Maternal Plasma Apelin Concentrations in Preeclampsia

Background. Preeclampsia is a hypertensive disorder that complicates 3–7% of pregnancies. The development of preeclampsia has not been completely elucidated and current therapies are not broadly efficacious. The apelinergic system appears to be involved in hypertensive disorders and experimental studies indicate a role of this system in preeclampsia. Thus, an epidemiological evaluation of apelin protein concentration in plasma was conducted in case–control study of pregnant women. Methods. Data and maternal plasma samples were collected from pregnant women with confirmed preeclampsia (n = 76) or normotensive controls (n = 79). Concentrations of apelin peptides were blindly measured using enzyme-linked immunosorbent assay. Data were subjected to statistical analyses. Results. Plasma apelin concentrations, measured at delivery, were lower in preeclampsia cases compared with controls (mean ± standard deviation: 0.66 ± 0.29 vs. 0.78 ± 0.31 ng/mL, p = 0.02). After controlling for confounding by maternal age, smoking status, and pre-pregnancy body mass index, odds of preeclampsia were 48% lower for women with high versus low plasma apelin (≥0.73 vs. <0.73 ng/mL) concentrations. Conclusion. Reduced circulating apelin peptides may be associated with preeclampsia. The apelinergic system should be further investigated to elucidate its role in preclampsia and other hypertensive maternal disorders.     

Differential regulation of TNF receptors in maternal leukocytes is associated with severe preterm preeclampsia

We tested the hypothesis that maternal peripheral blood leukocytes contribute to elevated levels of soluble TNF receptors (sTNFR) in preeclampsia (PE) with concomitant intrauterine growth restriction (IUGR). TNFR1 and TNFR2 were evaluated in a cross-sectional study comparing preeclamptic (n?=?15) with or without IUGR versus normotensive pregnant women (PREG, n?=?30), and non-pregnant controls (Con; n?=?20). Plasma levels of sTNFR1 were higher in PE (1675.0?±?227.1?pg/mL) compared with PREG (1035.0?±?101.1?pg/mL) and Con (589.3?±?82.67?pg/mL), with the highest values observed in PE with IUGR (2624.0?±?421.4?pg/mL; n?=?6). Plasma sTNFR2 was higher during pregnancy (PE: 1836.0?±?198.7?pg/mL; PREG: 1697.0?±?95.0?pg/mL) compared with Con (598.3?±?82.7?pg/mL). Urinary levels of sTNFR1 and sTNFR2 were higher in PE and PREG compared with the Con group. Abundance of TNFR1 mRNA in peripheral blood leukocytes was strongly correlated with plasma levels of sTNFR1 in PE. However, TNFR2 mRNA accumulation in leukocytes did not correlate with sTNFR2 plasma levels. The level of sTNFR1 in plasma was correlated with body weight of the newborn (r?=??0.56). The data suggest that maternal leukocytes contribute to sTNFR1 levels in plasma in association with decreasing newborn weight and PE with concomitant IUGR.     

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.     

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.     

Doppler sonography of the uterine and the cubital arteries in normal pregnancies, preeclampsia and intrauterine growth restriction: evidence for a systemic vessel involvement

AIMS: The decrease in uterine resistance during normal pregnancy is known to be related to invading trophoblast cells which derive from placental tissue. Uterine and peripheral resistance is elevated in preeclampsia. The aim of the present study was to prospectively examine uterine and peripheral resistance in pregnancies complicated by preeclampsia (PE), fetal intrauterine growth restriction (IUGR) and pregnancy induced hypertension (PIH). METHODS: Sixty-seven women with normal pregnancies, 17 with PE, 12 with IUGR underwent Doppler sonographic investigation of the uterine and the cubital arteries. The Pulsatility Index (PI) was calculated for each vessel. Statistical analysis was performed and a P-value <0.05 was considered significant. RESULTS: Patients with preeclampsia and IUGR showed a significant higher resistance at the placental (mean PI 1.267 and 1.063), nonplacental (mean PI 1.631 and 1.124) and cubital artery (mean PI 3,777 and 3.995) compared to the normal pregnancy group (mean PI 0.678; 0.859 and 2.95 respectively). Mean birth weight in the PE group was 1409 g, in the IUGR group 1649 g and 3419 g in the normal pregnancy group. CONCLUSIONS: Pregnancies with IUGR are associated with elevated peripheral resistance in the maternal arterial system as seen in pregnancies with preeclampsia. Our findings encourage to further investigate the maternal vascular system in high risk pregnancies.     

Myeloperoxidase in the plasma and placenta of normal pregnant women and women with pregnancies complicated by preeclampsia and intrauterine growth restriction

Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n?=?40) and those who subsequently developed PE (n?=?20), IUGR (n?=?11) or both (PE?+?IUGR, n?=?8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE?+?IUGR. The MPO concentrations were measured using ELISA. Women with PE?+?IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE?+?IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE?+?IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

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.     

Correlation of fetal DNA levels in maternal plasma with Doppler status in pathological pregnancies

OBJECTIVES: To evaluate whether intrauterine growth restriction (IUGR) as seen in preeclampsia is associated with high levels of fetal DNA in maternal circulation, and whether fetal DNA is related to altered uterine and/or umbilical artery Doppler velocimetry. METHODS: Fetal DNA quantification was performed by real-time PCR on SRY sequences in 64 male-bearing pregnant women with IUGR and/or preeclampsia and 89 controls. RESULTS: Fetal DNA content was significantly elevated in IUGR pregnancies similar to preeclampsia and correlated with altered umbilical Doppler velocimetry, while no correlation was found with uterine Doppler status. CONCLUSION: Increased fetal DNA levels in maternal plasma may be a sign of placental or fetal pathology even in the presence of normal uterine Doppler velocimetry, allowing a more precise diagnostic evaluation. The finding that elevated fetal DNA in IUGR pregnancies correlates with abnormal umbilical Doppler velocimetry suggests that fetal DNA release is associated more with fetal chronic hypoxia than with fetal size.     

Plasma- and urine concentrations of nitrite/nitrate and cyclic Guanosinemonophosphate in intrauterine growth restricted and preeclamptic pregnancies

Background: The Nitric Oxide (NO) system plays an important role in the establishment and maintenance of the feto-placental circulation. Research on the pathogenesis of preeclampsia in several studies has established the involvement of the NO-system in preeclampsia and fetal intrauterine growth restriction (IUGR). In the presented study we analyzed the urine and plasma concentrations of nitrite/nitrate, the stable endproducts of NO and its second messenger, cyclic Guanosinemonophosphate (cGMP) in normal, preeclamptic and IUGR pregnancies. Patients and methods: In total 76 patients were investigated in a prospective study for repeated determination of plasma and urinary levels of nitrate/nitrite and cGMP: 49 patients with a normal course of pregnancy, 14 patients with fetal IUGR and 13 patients with preeclampsia were included into the study. Plasma and urine Nitrite/Nitrate-concentrations were determined using a Colorimetric Assay (Cayman Inc., USA), concentrations of the second messenger cGMP in plasma and urinary samples were determined with a J¹²⁵-Radio-Immuno-Assay (ibl Inc., Germany). The Stat View Program (Abacus Concepts, Inc., Berkeley, CA, 1992–1998) was used for statistical analysis, a P value <0.05 was considered significant. Results: Analyzing the data with the Kruskall–Wallis test a significance was reached for Plasma Nitrite/Nitrate (P=0.0236), plasma cGMP (P=0.004) and urinary nitrite/nitrate (P=0.032). No significance was seen for urinary cGMP (P=0.656). Comparing normal and preeclamptic and normal and IUGR pregnancies the following significant differences were seen (Mann–Whitney U test): In preeclamptic pregnancies urine nitrite/nitrate concentration was significantly lower compared to normal pregnancies (P=0.009) No significant difference between normal and preeclamptic pregnancies for plasma nitrite/nitrate (P=0.819) and plasma–cGMP (P=0.072) could be observed. In IUGR pregnancies plasma nitrite/nitrate and the plasma–cGMP concentrations were both significantly lower compared to normal pregnancies (P=0.0077 and 0.0066) in IUGR-pregnancies. No significance was reached when analyzing urine-Nitrite/Nitrate (P=0.7). Conclusion: Whereas in preeclampsia a reduced urinary nitrite/nitrate was analyzed, IUGR pregnancies showed reduced plasma nitrite/nitrate and cGMP. A reduced release of NO into the maternal circulation might lead to the presented findings and be involved in the pathogenesis of preeclampsia and fetal IUGR.     

Increased plasma soluble fms-like tyrosine kinase 1 and endoglin levels in pregnancies complicated with preeclampsia

Background.?Increased maternal plasma levels of proinflammatory cytokines as well as the anti-angiogenic agents soluble fms-like tyrosine kinase 1 (sFlt-1) and endoglin (sEng) are associated with promoting vascular dysfunction leading to the maternal syndrome of preeclampsia.

Objective and method.?Nulliparous women complicated with preeclampsia (n = 29) and their corresponding controls (n = 29) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil-Ecuador were requested to participate in a study evaluating plasma levels of soluble anti-angiogenic factors (sFlt-1 and sEng) and pro-inflammatory cytokines: interleukin 6 (IL-6), interleukin 8 (IL-8), granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor-alpha (TNF-α). Maternal and neonatal data were also assessed and compared among the study groups.

Results.?No significant differences in either maternal baseline or delivery characteristics were observed among the study groups. Compared with controls, preeclamptic women exhibited higher plasma levels of sFlt-1 (19.0 ± 15.1 vs. 12 ± 8.3 ng/mL) and of sEng (20.4 ± 9.9 vs.15.9 ± 9.4 ng/mL); respectively, p < 0.05. Women with severe disease displayed higher sFlt-1 and sEng levels when compared with mild ones (34.5 ± 11.6 vs. 9.5 ± 1.6 ng/mL, and 29.5 ± 9.0 vs. 14.8. ± 5.2 ng/mL, respectively; p < 0.001). In contrast, women with preeclampsia exhibited significant lower IL-8 and G-CSF levels compared with controls. No differences existed between either group in IL-6 levels or TNF-α.

Conclusion.?Consistent with previous reports, increased sFlt-1 and Eng levels in maternal plasma is consistent with vascular dysfunction found in gestations complicated with 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.     

REDUCED RED BLOOD CELL DEFORMABILITY,AN INDICATOR FOR HIGH FETAL OR MATERNAL RISK,IS FOUND IN PREECLAMPSIA AND IUGR

Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.     

The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism

Insulin resistance in late pregnancy increases nutrition availability in maternal circulation. Moreover, it is the leading cause of oxidative stress in pregnant women. Herein, we aimed to define the correlation between insulin resistance, serum inducible nitric oxide (iNOS) and serum lipid levels in patients with intrauterine growth retardation (IUGR) pregnancies and controls. We performed a cross sectional study of IUGR pregnancies uncomplicated with preeclampsia as cases and age, body mass index, parity and gestational age matched pregnant women as controls. We quantified serum insulin, fasting blood sugar (FBS), iNOS and lipid profile of the cases and controls. Serum total cholesterol and LDL-C were significantly lower when serum iNOS, FBS, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels were significantly higher in patients with IUGR pregnancies. There was not any significant difference in serum iNOS levels between patients and controls (12.4?±?2.1 vs. 11.1?±?1.9; p?=?0.52) after multiple adjustment for HOMA-IR. Serum iNOS levels were significantly correlated with maternal serum insulin, triglyceride and HOMA-IR levels in patients with IUGR pregnancies when there was not such a correlation in controls. We showed a positive correlation between insulin resistance and markers of oxidative stress like iNOS in IUGR pregnancies.     

Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction

Objective.?To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them.

Methods.?Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined.

Results.?Umbilical NO concentrations in SGA infants (mean ± SD; 176.2 ± 75.8 μmol/L) were significantly greater than in AGA infants (143.4 ± 39.2 μmol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 ± 4.4 pmol/mL and 14.5 ± 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups.

Conclusions.?We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.     

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation.

Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n?=?20), and their controls matched for parity, and maternal and gestational age.

Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay.

Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9?pg/mL, artery and vein, respectively, p?0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0?±?298.4 versus 690.3?±?401.9 mIU/L, artery and vein, respectively, p?<?0.05), and free β-hCG (mean: 33.9?±?4.3 versus 17.2?±?4.0 and 30.1?±?5.2 versus 13.7?±?3.3?ng/mL, artery, and vein respectively, p?<?0.05).

Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.