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.     

Association of Antithrombin Activity with Plasma Aldosterone Concentration and Plasma Renin Activity in Pregnant Women

Objective. To test the hypothesis that the blood antithrombin (AT) activity is correlated with the plasma aldosterone concentration (PAC), the plasma renin activity (PRA), and/or the PAC-to-PRA ratio during the late stage of pregnancy. Methods. The AT activity, PAC, and PRA were determined within 7 days prior to delivery in 47 women, consisting of 30 normotensive and 6 hypertensive women with singleton pregnancies and 11 normotensive women with twin pregnancies. Results. The median values of the 47 women were 86% of the normal activity level for the AT activity, 442 pg/mL for the PAC, 3.7 ng/mL/h for the PRA, and 108 pg/mL per ng/mL/h for the PAC-to-PRA ratio. Women with an AT activity ≤86% had a significantly lower PRA and a higher PAC-to-PRA ratio than women with an AT activity >86% (3.5 ± 3.0 vs. 6.6 ± 4.7 ng/mL/h for PRA, p = 0.008; 156 ± 109 vs. 97 ± 46 pg/mL per ng/h for PAC-to-PRA ratio, p = 0.021). The AT activity was significantly correlated positively with the PRA and negatively with the PAC-to-PRA ratio. Conclusions. The existence of a common pathophysiological background between a reduced AT activity and a reduced PRA during the late stage of pregnancy was suggested.     

The effect of the D1-C785T polymorphism in the type 1 iodothyronine deiodinase gene on the circulating thyroid hormone levels in Romanian women with preeclampsia. Association with the degree of severity and pregnancy outcome of preeclampsia

Aim: To investigate the biochemical and genetic thyroid status in women with preeclampsia by the determination of serum FT3 and FT4 levels in association with D1-C785T genotypes. Methods: We genotyped using PCR–RFLP methods 50 women with preeclampsia and 50 normotensive pregnant women. Results: FT3 levels (pg/ml, 2.63?±?0.56 vs. 2.91?±?1.41) were low, and FT4 levels (ng/dl, 1.11?±?0.3 vs. 0.88?±?0.14) were high in women with preeclampsia compared to normal pregnant women. The association with severe preeclampsia was stronger for the homozygous T/T genotype (OR 6.57, p?=?0.029). Women with preeclampsia with the D1-T785 mutated allele had lower FT3 levels (pg/ml, 2.31?±?0.81 vs. 3.04?±?0.39, p?<?0.001), higher FT4 levels (ng/dl, 1.32?±?0.87 vs. 0.84?±?0.24, p?=?0.009) than women with preeclampsia with the D1-C/C genotype. Significant decrease in serum FT3 levels in positive women with severe preeclampsia compared to women negative for this genetic variation (pg/ml, 1.59?±?0.74 vs. 2.77?±?0.23, p?=?0.003) was observed. Women with severe preeclampsia, positive for the mutated T785 allele, delivered at a significantly lower gestational age (31.75?±?3.69 vs. 38.66?±?3.21 weeks, p?=?0.035) neonates with a lower birth weight (1861.11?±?869.9 vs. 3500?±?424.26?g, p?=?0.023) compared to women negative for the same allele. Conclusions: Thyroid hormone levels and the D1-C785T polymorphism, alone or in combination, correlate with the severity of preeclampsia. The D1-C785T polymorphism influences the outcome of pregnancy in severe preeclampsia.     

Serum Inhibin A Level in Preeclampsia and Normotensive Pregnancy

Objective: To compare serum inhibin A levels in pregnancy complicated by preeclampsia and in normotensive pregnancy. Materials and methods: Blood samples were taken from 60 women. Thirty women were diagnosed with preeclampsia, and 30 women had normotensive pregnancies. Both groups were matched for gestational age. Blood samples were collected in plain tubes, centrifuged, and stored at –80°C until analyzed. All serum samples were measured for inhibin A level by enzyme-linked immunosorbent assay (ELISA). Results: Inhibin A levels were greater in the preeclampsia group (1229.7 ± 537.5 pg/mL) than in the normotensive group (839.1 ± 370.0 pg/mL, p = 0.002). Conclusions: Levels of inhibin A in the preeclampsia group were greater than in the normotensive group.     

Preeclampsia and superimposed preeclampsia: The same disease? The role of angiogenic biomarkers

Objective: We aimed to compare sFlt-1 and placental growth factor (PlGF) levels and the sFlt-1/PlGF ratio between women with preeclampsia and superimposed preeclampsia to, respectively, normotensive and chronic hypertensive ones. Study design: We performed a prospective two-armed cohort in a tertiary teaching hospital in Sao Paulo, Brazil, including 37 normotensive and 60 chronic hypertensive pregnant women. We assessed the serum levels of sFlt-1 and PlGF at 20, 26, 32, and 36 gestational weeks by enzyme-linked immunosorbent assay. Main outcome measures: Having preeclampsia and superimposed preeclampsia. Results: Among normotensive and chronic hypertensive pregnancies, 4 (10.8%) and 14 (23.3%) women developed preeclampsia and superimposed preeclampsia, respectively. Compared with those who remained normotensive, the preeclampsia women presented higher sFlt-1 levels at 32 gestational weeks (4323.45 pg/mL vs. 2242.04 pg/mL, p = 0.019), lower PlGF levels at 20 (183.54 pg/mL vs. 337.38 pg/mL, p = 0.034), 32 (169.69 pg/mL vs. 792.53 pg/mL, p = 0.001), and 36 gestational weeks (252.99 pg/mL vs. 561.81 pg/mL, p = 0.029), and higher sFlt-1/PlGF ratios at 26 (9.02 vs. 1.84, p = 0.004), 32 (23.61 vs. 2.55, p = 0.001), and 36 gestational weeks (49.02 vs. 7.34, p = 0.029). On the other hand, compared with those who remained chronic hypertensive, the superimposed preeclampsia women only presented a higher sFlt-1/PlGF ratio at 32 gestational weeks (9.98 vs. 2.51, p = 0.039). Conclusion: Although angiogenic imbalance is clearly related to preeclampsia, it seems to play a more modest role in superimposed preeclampsia, in which other mechanisms should also be investigated.     

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.     

Prostacyclin and Thromboxane Levels in Women with Severe Preeclampsia Undergoing Magnesium Sulfate Therapy During Antepartum and Postpartum Periods

Objective: To study effects of magnesium sulfate (MgSO₄) on prostacyclin (PGI₂) and thromboxane A₂ (TXA₂) levels in women with severe preeclampsia during antepartum and postpartum periods. Methods: Women with severe preeclampsia were randomized into two groups. Patients in Group A were continuously infused with MgSO₄ for 24 hours postpartum. In Group B, MgSO₄ administration was discontinued when urinary output was of ≥100 ml/hr for 2 consecutive hours. Patient demographic data were collected. Venous blood was drawn at time of MgSO₄ administration and 24 hours after delivery. Plasma levels of 6-keto-PGF1α and TXB₂, stable metabolites of PGI₂ and TXA₂, were measured by enzyme-linked immunosorbent assay (ELISA). Data are presented as mean ± SE, and analyzed by paired t-test. Results: A total of 50 patients were recruited, with 27 in Group A and 23 in Group B. There were no statistical differences for demographic data between the two groups with regards to maternal age; gestational age; systolic and diastolic blood pressures at admission, 12 hours postpartum, and 24 hours postpartum; and mode of delivery. Platelet counts were all within the normal range at the time of enrollment. MgSO₄ was administered for an average of 10 hours postpartum in Group B. Maternal blood pressures returned to normal or close to normal levels in both groups at 24 hours postpartum. 6-keto PGF1α levels were significantly decreased 24 hours after delivery compared with the levels at enrollment in both groups, (Group A: 98 ± 13 vs. 180 ± 28 pg/mL; Group B: 142 + 17 vs. 194 ± 31 pg/mL, p < 0.05, respectively). However, there was no difference detected between the two groups. TXB₂ levels were not different between group A and Group B at the time of enrollment, 38 ± 9 vs. 33 ± 8 pg/mL, and 24 hours postpartum, 26 ± 5 vs. 25 ± 3 pg/mL, respectively. Conclusions: Administration of MgSO₄ does not affect prostacyclin and thromboxane levels in the maternal circulation in women with preeclampsia during antepartum and postpartum periods. We speculate that a higher level of prostacyclin before delivery may reflect compensatory effects of this vasodilator to offset increased maternal blood pressure during pregnancy.     

HEAT SHOCK PROTEIN 70 IS NOT INCREASED IN WOMEN WITH SEVERE PREECLAMPSIA

Objective: The purpose of this study is to determine if heat shock protein 70 (Hsp 70), a marker of cellular stress, is elevated in pregnancies complicated by severe preeclampsia. Methods: Maternal blood was collected from women with severe preeclampsia (n=47) matched for delivery gestational age to normotensive pregnant controls (n=51). Hsp 70 concentrations were measured by standard ELISA techniques. Data were analyzed with the Student's t-test and chi-square test. Main outcome measures: The primary outcome measured was Hsp 70 concentrations. Our hypothesis prior to data collection was that HSP 70 would be increased in women with severe preeclampsia. Results: Compared with normotensive women, those with severe preeclampsia had similar maternal age, parity, delivery gestational age, maternal weight, and ethnicity. There was no difference in mean concentrations of Hsp 70 between women with severe preeclampsia and controls (35.4±96.7 vs. 30.1±11.5, p=0.80). Similar numbers of women with severe preeclampsia (n=28) and controls (n=30) had Hsp 70 concentrations below the 0.02 ng/dL level of detection (chi-square value=0.024, p=0.88). Conclusion: Hsp 70 concentrations are not elevated in women with severe preeclampsia.     

A comparison of serum androgens in pre-eclamptic and normotensive pregnant women during the third trimester of pregnancy

Objective: To compare the serum androgens level during the third trimester of pregnancy between normotensive and pre-eclamptic women. Method: A case–control study was performed on 64 pregnant women with the gestational age of 28–34 weeks. 32 women were pre-eclamptic (case group), and 32 women were normotensive till term gestation (control group). The serum level of androgens including sex hormone binding globulin (SHBG), total and free testosterone, androstenedione (ADD), and dehydroepiandrosterone sulfate (DHEA-S), were compared between the two groups. Results: The women of the two groups had no statistically significant difference according to age, gestational age, BMI (body mass index), parity and fetal sex. Serum level of SHBG (90.86 ± 9.30 vs. 55.86 ± 8.02 nmol/l, p = 0.02), total testosterone (3.70 ± 0.57 vs. 2.06 ± 0.24 ng/ml, p = 0.01), free testosterone (1.28 ± 0. 17 vs. 0. 74 ± 0.07 pg/ml, p = 0.01), and ADD (2.47 ± 0.10 vs. 2.17 ± 0.10 ng/ml, p = 0.04), was higher in the pre-eclamptic women. However, there was no difference between the two groups for DHEA-S (0.75 ± 0.18 vs. 0.51 ± 0.08 μg/ml, p = 0.19). Conclusion: Serum androgen levels during third trimester of pregnancy are higher in pre-eclamptic women and this may propose an effect of androgens in the pathogenesis of pre-eclampsia.     

Glucose Tolerance in Women 24 h Postpartum Is Related to Blood Pressure,Anthropometric Data,and Adipokine Serum Levels

Objectives. To characterize glucose tolerance and adipokine serum levels in a cohort of women shortly after delivery. Study Design. A study population of healthy pregnant women (n = 65) was invited to undergo a standardized oral glucose tolerance test within 24 h after delivery at the University Hospital of Leipzig. As controls, 30 nonpregnant healthy, lean women were studied. Glucose, insulin, proinsulin, c-peptide, leptin, adiponectin, and soluble leptin receptor levels were compared in cases and controls by using the Mann–Whitney U two-sample statistics and correlation according to Spearman. Results. As compared to normal glucose tolerant (NGT) women postpartum, fasting c-peptide levels were significantly higher (NGT mothers = 0.23 nmol/L, controls: 0.49 nmol/L, p < 0.001), whereas proinsulin serum levels were significantly lower in nonpregnant controls (NGT mothers = 1.37 pmol/L, controls = 1.00 pmol/L, p = 0.05). Considering fasting adiponectin values, postpartum adiponectin was significantly decreased compared with controls (NGT mothers = 6.9 μg/L, controls = 8.9 μg/L, p = 0.05). Fasting serum levels of leptin (NGT mothers = 17 ng/mL, controls = 10.6 ng/mL, p < 0.009) and soluble leptin receptor (NGT mothers = 34.4 ng/mL, controls = 17.7 ng/mL, p < 0.001) were increased postpartum. Conclusion. We found significantly lower adiponectin and higher leptin sera levels in women postpartum as compared to nonpregnant women. In addition, adipokine serum levels shortly after delivery were related to parameters of adiposity and glucose tolerance. We hypothesize that women in the post-delivery period exhibit biochemical features resembling metabolic syndrome, impaired glucose tolerance, and derangement of the adipokine system.     

Postpartum Course of Gestational Hypertension and Preeclampsia

Background: New onset hypertension (gestational hypertension and preeclampsia) complicates 6–8% of pregnancies and usually resolves postpartum, but the time to normalization of blood pressure (BP) in the postpartum period is not known. Methods. We performed a retrospective cohort study of previously normotensive women who developed gestational hypertension or preeclampsia, and determined the number of weeks postpartum to BP normalization. Results: 62 women with no history of hypertension prior to pregnancy were included, age 35.3 ± 7.1 years. Hypertension developed at gestational age 15–40 weeks; 45% developed hypertension within 3 days of delivery, 52% developed hypertension 1–22 weeks prior to delivery, and 5% had onset only postpartum. Infants were born at gestational age 35.15 ± 4.7 weeks. Average BP at treatment initiation was 162/95 mm Hg. Preeclampsia and/or HELLP syndrome was diagnosed in 48%. Most were treated with BP medication in the puerperium. In those whose BP normalized, time to normalization was 5.4 ± 3.7 weeks. Those who remained hypertensive beyond 6 months (19%) were older (38.8 years vs. 34.4, p = 0.018). Three women had secondary hypertension; primary hyperaldosteronism was diagnosed in 2 women and renovascular hypertension in 1. Conclusion: Hypertension presenting in pregnancy normalized postpartum in 81% of this cohort, in most by 3 months. Those who remained hypertensive at 6 months postpartum tended to be older than patients whose BP normalized. Secondary hypertension was detected and surgically corrected in 3 patients. Further studies are needed to characterize those most likely to benefit from postpartum antihypertensive treatment and to guide management.     

Serum leptin levels and the severity of preeclampsia

The aim of this study was to evaluate the serum leptin levels in preeclampsia patients and in normotensive pregnant women, as well as, to assess an association with the severity of the disease. A cross-sectional study was carried out in 14 patients with mild preeclampsia, 12 with severe preeclampsia, and in 32 normotensive pregnant women during the third trimester of pregnancy. Rigorous criteria of selection were considered. The leptin levels were tested by an enzyme-linked immunosorbent method. There were no significant differences in serum leptin concentrations between the patients with mild preeclampsia [13.6±11.2 (95% CI, 7.7–19.4) ng/mL], severe preeclampsia [14.8±11.5 (95% CI, 8.2–21.3) ng/mL] and normotensive pregnant women [12.5±7.9 (95% CI, 9.7–15.2) ng/mL]. In conclusion, serum leptin levels were similar in the patients with different grades of preeclampsia and normotensive pregnant women. Received: 30 November 1999 / Accepted: 16 March 2000     

Homocysteine and Cellular Fibronectin are Increased in Preeclampsia,not Transient Hypertension of Pregnancy

Objective. The objective of this study was to confirm that endothelial dysfunction is present in preeclampsia and absent in transient hypertension of pregnancy, and to determine whether the cardiovascular risk factor homocysteine is associated with the degree of endothelial dysfunction.

Methods. We measured cellular fibronectin (as a marker of endothelial injury) and total plasma homocysteine in samples collected at the time of admittance to labor and delivery in 17 women with preeclampsia (increased blood pressure, proteinuria, and hyperuricemia), 16 women with transient hypertension of pregnancy (only increased blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was matched by prepregnancy body mass index, race, and gestational age at delivery to one subject with transient hypertension of pregnancy and two controls.

Results. Cellular fibronectin was found to be significantly increased in women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (22.9±14.1 μg/mL versus 10.9±5.4 and 10.1±6.2 μg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was also significantly increased in the women with preeclampsia compared to subjects with transient hypertension of pregnancy or normal pregnant women (8.3±2.5 μM versus 5.5±2.2 and 5.4±3.4 μM respectively, p<0.01). However, contrary to our hypothesis, there was no apparent association between cellular fibronectin and homocysteine.

Conclusions. The increased concentrations of homocysteine observed in preeclampsia are not a general feature of all hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is present in preeclampsia and is not evident in transient hypertension of pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not explained by the increase in homocysteine concentrations observed.     

Women with Preeclampsia Have Increased Serum Levels of Pregnancy‐Associated Plasma Protein A (PAPP‐A), Inhibin A,Activin A and Soluble E‐selectin

Objective. Poor placentation in early pregnancy is thought to lead to an excessive maternal systemic inflammatory response, which causes the maternal syndrome of preeclampsia. The aims of this retrospective study were to confirm old reports of increased blood levels of pregnancy‐associated plasma protein A (PAPP‐A) in preeclampsia and how its levels correlate with the levels of other placental and endothelial proteins that are reported to be elevated in preeclampsia. Methods. Nineteen women with preeclampsia symptoms were matched with 19 normal pregnant controls for gestational age, maternal age, and parity. PAPP‐A, placental pregnancy‐specific β₁‐glycoprotein (SP1), inhibin A, activin A, and sE‐selectin were measured in serum using specific ELISAs. Results. Maternal serum levels of PAPP‐A, inhibin A, activin A and sE‐selectin were increased in women with preeclampsia (mean 157.7 vs. 76.85 mIU/mL, p=0.005; 3.08 vs. 1.51 ng/mL, p=0.002, 32.36 vs. 3.77 ng/mL, p<0.001 and 62.15 vs. 46.37 ng/mL, p=0.02 respectively), compared to controls. Serum levels of SP1 were not altered in preeclampsia. PAPP‐A (r=0.636, p<0.01) had a positive correlation with sE‐selectin in patients with preeclampsia. Serum inhibin A and activin A had a significant positive correlation with each other in preeclampsia. Conclusions. Raised levels of PAPP‐A in preeclampsia confirm earlier reports. Activin A showed the highest increase over the controls and is thus likely to be a better serum marker for this pathology than the other markers that were tested.     

Preeclampsia in women with chronic kidney disease

Objective: Women with chronic kidney disease have an increased risk of developing preeclampsia and its severe complications. Currently, there are no assessments available in order to quantify such risk. The aim of the study is to establish the incidence of superimposed preeclampsia in women with chronic kidney disease according to Serum creatinine (SCr) level. Methods: Pregnant women with chronic kidney disease were retrospectively identified from January 2000 to July 2010. We defined two groups according to SCr: Group 1: SCr ≤ 125 µmol/l; Group 2: SCr > 125 µmol/l. Incidence of preeclampsia, early preeclampsia (delivery <34 weeks), gestational age (GA) at diagnosis and delivery outcome were assessed. Results: Ninety-three nephropatic women were considered for the analysis. Group 2 (n?=?14) compared with Group 1 (n?=?79) had an increased incidence of preeclampsia (78.6% vs. 25.3%; p?<?0.0001), an increased rate of pregnancy complications as early preeclampsia (82% vs. 38%; p?<?0.03), a lower GA at diagnosis (29?±?2 vs. 33?±?1 weeks; p?<?0.04) and a lower GA at delivery (30?±?2 weeks vs. 34?±?1; p?<?0.04). Conclusion: Women with chronic kidney disease and an increased creatinine threshold have a high risk of developing preeclampsia and delivering preterm.     

Antepartum and postpartum maternal plasma levels of E-selectin and VE-cadherin in preeclampsia,gestational proteinuria and gestational hypertension

Objective.?To investigate the alterations of maternal antepartum and postpartum plasma levels of sE-selectin and VE-cadherin in normotensive pregnant women, women with preeclampsia (PE), gestational hypertension (GH), and gestational proteinuria (GP).

Methods.?A total of 37 pregnant women were included in the present study; 12 with PE, 10 with GH, 5 with GP, and 10 controls. sE-selectin and VE-cadherin levels were assessed in maternal plasma at three periods; before delivery, 3–6 days after delivery, and 12–14 weeks postpartum.

Results.?Women with severe preeclampsia (SPE) and GP had significantly higher plasma sE-selectin levels as compared to controls in all three periods of sampling. In the GH group, sE-selectin levels did not differ from controls. During the study, even after 12 weeks postpartum, the plasma sE-selectin levels remained unchanged in all preeclamptic groups (PE, GH, and GP). There was no difference in VE-cadherin levels between women with preeclampsia (PE, GH, and GP) and normal pregnancies.

Conclusions.?We found no changes in VE-cadherin levels in preeclamptic groups. Increased antepartum and postpartum levels of sE-selectin in women with SPE and GP suggest that endothelial dysfunction may be one of the key processes in the pathogenesis of PE and the underlying mechanism, as well, that links PE with cardiovascular disease in later life. GP, also, appears to be a mild variant of PE.     

Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls

Aims. To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR).

Methods. Twenty-two normal pregnant women were compared with 22 women diagnosed with gestational diabetes mellitus (GDM). Serum adiponectin levels were measured at the time of the glucose challenge test as well as in the immediate postpartum period and the correlation of adiponectin to HOMA-IR was performed.

Results. Adiponectin was significantly lower in women with GDM than in controls during pregnancy (5381 vs. 8449 ng/dl, p = 0.004), as well as postpartum (3278 vs. 6958 ng/ml, p = 0.002). A significant reduction in adiponectin (3278 vs. 5381 ng/ml, p = 0.002) was observed postpartum in GDM women but not in controls. Using a lower cut-off value of 5253 ng/ml, maternal adiponectin could exclude GDM with a sensitivity of 86.4% and a specificity of 59.1% (area under the curve = 0.752, standard error = 0.77, 95% confidence interval 0.601–0.903, p = 0.004). Adiponectin levels during pregnancy were negatively correlated with HOMA-IR (r = ?0.375, p = 0.012).

Conclusion. GDM is associated with decreased serum adiponectin levels both in pregnancy as well as postpartum. Adiponectin is negatively correlated to HOMA-IR. A reduction in maternal adiponectin after delivery indicates a significant placental contribution to adiponectin production.     

Pathological Uterine Perfusion in the Second Trimester Is Not Associated with Neutrophil Activation

Objective: Preeclampsia and intrauterine growth retardation (IUGR) are associated with elevated concentrations of myeloperoxidase (MPO) and polymorphonuclear (PMN) elastase, which indicate maternal neutrophil activation. The aim of the study was to measure maternal MPO and PMN elastase plasma concentrations in second trimester pregnancies with pathological uterine perfusion that are a high risk group for preeclampsia and IUGR, and compare them to normal controls. Methods: The study includes 25 pregnancies with normal and 25 pregnancies with pathological uterine perfusion. In both groups, doppler‐sonographic measurement of uterine perfusion was performed in the twenty‐first week of gestation. Maternal plasma concentrations of MPO and PMN elastase were measured using a specific ELISA for both enzymes. Results: The plasma MPO concentration of pregnant women with normal perfusion did not differ significantly from that of the group with pathological perfusion (27.4 ± 3.3 vs. 23.7 ± 2.0 ng/mL). Likewise, the plasma PMN elastase‐concentration also did not show a significant difference between the groups (5.7 ± 0.5 ng/mL normal vs. 8.0 ± 1.0 ng/mL pathological). Patients with pathological perfusion that later developed preeclampsia or IUGR (9/25) showed unchanged MPO and PMN elastase values in the second trimenon compared to those with pathological perfusion and normal outcome. Conclusions: Pathological uterine perfusion in the second trimester was not associated with maternal neutrophil activation. The measurement of the MPO and PMN elastase concentration suggested that neutrophil activation in preeclampsia or IUGR is a secondary effect of the disease rather than a primary pathophysiological factor.     

The Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) polymorphisms in the pathogenesis of preeclampsia in Romanian women: association with the severity and outcome of preeclampsia

Objective: To check whether individual or combined mutated genotypes for Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) are associated with preeclampsia; to check the influence of the mutated genotypes on the degree of severity and perinatal outcome of preeclampsia. Methods: We genotyped 97 pregnant women (47 with preeclampsia and 50 normal pregnant women) using PCR-RFLP analysis. Results: The Val/Val (Mn-SOD) genotype (OR 5.99, p?=?0.004) but not the Gly/Gly (EC-SOD) genotype (OR 4.23, p?=?0.027) was significantly associated with preeclampsia. Higher frequency of both polymorphisms in women with preeclampsia (42.55%) compared to normal pregnant women (8%). Higher frequency of women diagnosed with PIH (27.27%, OR 4.31), mild (50%, OR 11.5) and severe preeclampsia (37.5%, OR 6.9) positive for both polymorphism compared to control women (8%). There was a statistically significant difference in gestational age at delivery according to Mn-SOD (Ala/Ala vs. Val/Val, 39?±?1.41 weeks vs. 32.77?±?3.7 weeks) and EC-SOD genotypes (Arg/Arg vs. Gly/Gly, 37.05?±?3.18 weeks vs. 31.5?±?3.84 weeks). There also was a statistically significant difference in birth weight according to Mn-SOD (grams, Ala/Ala vs. Val/Val, 3080?±?481.66 vs. 2376.92?±?916.88) and EC-SOD genotypes (grams, Arg/Arg vs. Gly/Gly, 2934.09?±?662.14 vs. 2080?±?721.19). Conclusions: Our study demonstrates a relationship between these two mutated genes, the clinical severity and the perinatal outcome of preeclampsia.     

Fibronectin is a Marker for Organ Involvement and may Reflect the Severity of Preeclampsia

Objective. We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia.

Study design. Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester.

Results. In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 ± 0.06 g/L in pregnancy week 16 and 0.43 ±0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 ± 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 ± 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 ± 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 ± 0.22 g/L (p=0.03)].

Conclusion. Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.