Preeclampsia is associated with an elevation of plasma sMet concentrations in the second trimester

Abstract

Objective: The aim of this study was to investigate the association between anti-angiogenic factor soluble c-Met (sMet) concentrations in maternal plasma and the risk of preeclampsia.

Methods: The pregnant women included in this study (1) had subsequent preeclampsia (n?=?52) and were compared to normal controls (n?=?104) at the time of amniocentesis (15–20 weeks); and (2) had preeclampsia (n?=?63) and were compared to normal controls (n?=?112) at the time of diagnosis of preeclampsia (29–40 weeks). sMet concentrations were measured by ELISA. Non-parametric statistics were used for analysis.

Results: Maternal plasma sMet concentrations were significantly higher in both women with subsequent preeclampsia (median: 1372.7?ng/ml versus 1100.5?ng/ml; p?=?0.036) and women with preeclampsia (median: 1651.9?ng/ml versus 1364.7?ng/ml; p?<?0.001) than in the controls. After adjusting for potential confounding factors, the risks of developing preeclampsia were as follows: adjusted odds ratio 2.5 (95% confidence interval, 1.2–5.2; p?=?0.016) for second trimester sMet concentration with a cut-off value of 1223.5?ng/ml and 4.4 (95% confidence interval, 2.2–9.1; p?<?0.001) for third trimester sMet concentration with a cut-off value of 1460.3?ng/ml.

Conclusion: Elevated maternal plasma sMet concentrations were independently associated with the increased risk of preeclampsia.     

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.     

Does preeclampsia have any adverse effect on fetal heart?

Objective: To determine whether preeclampsia causes fetal cardiac cell damage by assessing umbilical artery NT-proBNP, cardiac troponin I and homocysteine.

Methods: A cross-sectional study with 73 fetuses between 26 and 40 weeks of gestation was performed. Thirty-three healthy mothers’ fetuses were control group (Group I). While 12 mildly pre-eclamptic mothers’ fetuses constituted Group II, 28 fetuses of severe pre-eclamptic mothers were Group III.

Results: Umbilical cord mean NT-proBNP levels of Group I, II and III are 520.8?±?404.5 pg/ml; 664.2?±?215.9 pg/ml; and 1932.8?±?2979.5 pg/ml, respectively (p?=?0.0001). The number of neonates with NT-proBNP?>?500 pg/mL that indicates severe cardiac damage is higher in Group III (p?=?0.001). The mean homocysteine levels are also statistically significantly higher in Group III. Cardiac troponin I levels are not different between the groups (p?=?0.46).

Conclusion: Increased NT-proBNP and homocysteine might not only indicate some degree of in-utero cardiac cell damage but also feto–placental endothelial injury in the fetuses of severe pre-eclamptic mothers. Our finding that shows no evidence of correlation between cardiac troponin I levels with cell damage and endothelial injury requires further research.     

Evaluation of maternal serum progranulin levels in normotensive pregnancies,and pregnancies with early- and late-onset preeclampsia

Aims: To investigate the possible pathophysiological associations between progranulin (PGRN) and preeclampsia (PE), early-onset PE (EOPE) and late-onset PE (LOPE).

Study design: A cross-sectional study was designed to include consecutive patients with uncomplicated pregnancy (n?=?28), EOPE (n?=?30) and LOPE (n?=?22). Maternal levels of serum PGRN were measured with the use of an enzyme-linked immunosorbent assay kit.

Results: The mean serum PGRN level was significantly higher in women with PE compared to the control group (54.17?±?4.20?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001), in the LOPE group compared to the control group (51.63?±?4.61?pg/ml versus 42.37?±?5.64?pg/ml, p?<?0.001) and also in women with EOPE compared to women with LOPE (56.03?±?2.68?pg/ml versus 51.63?±?4.61?pg/ml, p?<?0.001). Serum PGRN was negatively correlated with gestational age at birth (r?= ?0.669, p?=?0.001) and birth weight (r?= ?0.653, p?=?0.001); and positively correlated with systolic (r?=?0.653, p?=?0.001) and diastolic blood pressure (r?=?0.601, p?=?0.001), C-reactive protein (r?=?0.519, p?=?0.001), uterine artery pulsatility (r?=?0.441, p?=?0.001) and resistance indices (r?=?0.441, p?=?0.001).

Conclusions: Serum PGRN levels increase significantly in women with PE as an indirect sign of placental dysfunction. This increase is even more prominent in women with EOPE. The serum PGRN in the third trimester is positively correlated with gestational age at birth and birth weight.     

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.     

Is serum placental growth factor more effective as a biomarker in predicting early onset preeclampsia in early second trimester than in first trimester of pregnancy?

Purpose

To determine whether maternal serum placental growth factor (PlGF) is more effective as a biomarker in predicting the occurrence of early onset preeclampsia in first trimester or early second trimester of pregnancy.

Methods

A prospective cohort study was conducted on women with singleton pregnancies, screened from the antenatal clinic. Serum PlGF estimation was done at 11–14 weeks of gestation on 1,244 women and at 22–24 weeks of gestation on 1,206 women from the initial study population. A cut-off value of <228 pg/ml for serum PlGF at 11–14 weeks of gestation and <144 pg/ml for serum PlGF at 22–24 weeks of gestation were determined by receiver operating characteristic (ROC) curve analysis for identifying pregnant women at risk of developing early onset preeclampsia (<32 weeks of gestation). Univariate logistic regression analysis was used to analyze the association between serum PlGF < 228 pg/ml at 11–14 weeks of gestation and <144 pg/ml at 22–24 weeks of gestation with the occurrence of early onset preeclampsia and odds ratio (OR) was computed. P value < 0.05 was considered statistically significant in this study.

Results

Maternal serum PlGF <144 pg/ml at 22–24 weeks of gestation had a stronger association (OR 18.83; 95 % CI 12.08–22.24; p = 0.000) than serum PlGF <228 pg/ml at 11–14 weeks of gestation (OR 2.76; 95 % CI 1.29–3.94; p = 0.007) with the occurrence of early onset preeclampsia. The sensitivity and specificity of serum PlGF <144 pg/ml at 22–24 weeks of gestation (84 and 78, respectively) were much higher than those of serum PlGF <228 pg/ml at 11–14 weeks of gestation (58 and 66, respectively) in predicting early onset preeclampsia.

Conclusion

Maternal serum PlGF may be more effective as a biomarker in early second trimester than in first trimester of pregnancy, in predicting the occurrence of early onset preeclampsia.     

Relationship between nulliparity and preeclampsia may be explained by altered circulating soluble fms-like tyrosine kinase 1

Objective: To test the hypothesis that the risk of preeclampsia in nulliparous women may be due to an anti-angiogenic state. Methods: Maternal serum samples obtained in the third trimester from nulliparous (n?=?86) and multiparous (n?=?165) singleton uncomplicated pregnancies were analyzed for levels of angiogenic factors – soluble fms like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) by enzyme-linked immunosorbent assay (ELISA). Results: For nulliparous and multiparous pregnancies, serum sFlt1 levels were 12?732?±?832 and 10?162?±?666 (p?=?0.020), serum PlGF levels were 215?±?15 and 249?±?14 (p?=?0.093) (all reported as mean SD in pg/ml) and mean ratios of sFlt1/PlGF were 93?±?12 and 62?±?5 (p?=?0.023), respectively. Adjustment for maternal age and fetal birth weight did not alter the results. Conclusions: Nulliparous pregnancies had higher circulating sFlt1 levels and sFlt1/PlGF ratios than multiparous pregnancies, suggesting an association with an angiogenic imbalance. Taken together with the pathogenic role of anti-angiogenic factors in preeclampsia, our data may be one explanation for the epidemiological observation that nulliparity is a risk factor for the development of preeclampsia.     

Tenascin C levels in patients with mild and severe preeclampsia

Objective: To determine the serum tenascin-C (TN-C) levels in cases with mild and severe preeclampsia.

Methods: Pregnant women were divided into three groups, namely healthy pregnants (Group 1, n?=?20), pregnants with mild preeclampsia (Group 2, n?=?20) and pregnants with severe preeclampsia (Group 3, n?=?20). The groups were formed so as to match each other in terms of gestational week. From each pregnant woman, pre- and post-delivery blood samples were obtained to measure serum TN-C levels. The data were evaluated using the Kruskall–Wallis variance analysis. For the obtained values of p?<?0.05, the groups were compared in pairs. A p value of <?0.017 was accepted as significant.

Results: In Groups 1, 2 and 3, the prepartum TN-C levels were 5.02?±?0.4?µg/ml, 12.8?±?2.9?µg/ml and 33.8?±?11.7?µg/ml, and in the postpartum TN-C levels were 4.7?±?0.1?µg/ml, 11.7?±?1.8?µg/ml and 50.6?±?33.8?µg/ml, respectively. There was a significant difference between the groups in terms of the prepartum and postpartum TN-C levels (p?<?0.017, Mann–Whitney U [MWU] test). There was also a significant difference in the prepartum TN-C levels between Groups 2 and 3 (p?<?0.017, MWU test).

Conclusions: The prepartum and postpartum TN-C levels were significantly higher in mild and severe preeclampsia than those in healthy pregnants.     

Increased homocysteine levels exist in women with preeclampsia from early pregnancy

Objective: The present prospective study examines the levels of maternal plasma folate, vitamin B₁₂ and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.

Methods: The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1?=?16th–20th weeks, T2?=?26th–30th weeks and T3?=?at delivery). Levels of folate, vitamin B₁₂ and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.

Results: Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B₁₂ levels were significantly higher in PE (p?<?0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p?<?0.05 for both) and T3 (p?<?0.01).

Conclusion: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.     

Angiogenic imbalance as a contributor to the pathophysiology of preeclampsia among black African women

Objective: The pathogenesis of preeclampsia remains unclear despite extensive research. Altered angiogenic balance has been hypothesized to play a significant role in the clinical manifestations of this syndrome. However this imbalance has not been investigated extensively among black African women. The aim of this study was to investigate the maternal levels of the angiogenic factors soluble vascular endothelial growth factor receptor 1 (sFLT1) and placental growth factor (PlGF) among black African women with preeclampsia.

Methods: A case control study was conducted in the Mthatha hospital complex in South Africa including 51 women with preeclampsia and 82 women with uncomplicated pregnancies. Blood samples were drawn from participants and serum was used to assess sFLT1, and PlGF levels quantified using specific enzyme linked immunosorbent assays. Non- parametric statistics were used for analysis.

Results: Black African women with preeclampsia were found to have significantly lower levels of PlGF (90.3?±?8.9?pg/ml versus 172.8?±?20.2?pg/ml; p?p?p?Conclusion: The results support an altered angiogenic balance may contribute to the pathogenesis/pathophysiology of preeclampsia among black African women as reported in other populations.     

Maternal levels of growth differentiation factor-15 in patients with preeclampsia

ABSTRACT

Objective: Growth differentiation factor-15 (GDF-15) is a stress-induced cytokine and related to the prognosis of cardiovascular diseases. Our purpose is to measure the maternal levels of GDF-15 in patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE).

Methods: This cross-sectional study was conducted including 72 pregnant women, 23 with normal pregnancies and 49 with preeclampsia (26 with EOPE and 23 with LOPE). Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits.

Results: The median serum GDF-15 level was found to be the highest in the EOPE group (EOPE: 441.7 pg/ml). The median serum GDF-15 levels were higher in women with preeclampsia than in the control group (309.7 pg/ml vs. 436.6 pg/ml, p: 0.009).

Conclusion: Our findings suggest GDF-15 increased as a response to endothelial injury caused by cytokines triggered by preeclampsia.     

Maternal psychosocial outcome after early onset preeclampsia and preterm birth

Objective.?To evaluate the impact of severe, early onset preeclampsia on long-term maternal psychosocial outcome after preterm birth.

Methods.?Women with severe, early onset preeclampsia before 32 weeks’ gestation (cases) admitted in a tertiary university referral center between 1993 and 2004, and women with preterm delivery without preeclampsia (controls), matched for age, parity, gestational age at delivery, ethnicity, and year of delivery. Women who consented to participation received three questionnaires in 2008 concerning depression (Zung Depression Scale: score range 0–20; 20 items with 2-point frequency scale: no?=?0 and yes?=?1), posttraumatic stress symptoms (Impact of Event Scale: score range 0–75; 15 items with 4-point frequency scale: not at all?=?0, rarely?=?1, sometimes?=?3 and often?=?5. Scores?>?19 are regarded as high symptom levels), and social aspects (Social Readjustment Rating Scale: selection of six items concerning relational aspects with husband/partner, employer, or future family planning).

Results.?Included in the study were 104 cases and 78 controls (response rate 79% and 58%, respectively). There was no difference in depression scores between cases (5.4 ± 4.0) and controls (5.4 ± 4.3). Patients with severe, early onset preeclampsia had significantly higher scores of posttraumatic stress symptoms (28.7 ± 8.6 vs. 25.7 ± 7.9). The majority of women among both cases and controls had high-posttraumatic stress symptom levels (88% vs. 79%). No differences could be found in relational aspects.

Conclusion.?Women with preterm birth due to severe, early onset preeclampsia experience more often posttraumatic stress symptoms on average 7 years after the pregnancy compared to women with preterm birth without preeclampsia.     

Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia

OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic proteins placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1 (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia. METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1, PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early control group of women at 24-32 weeks of gestation, in a late control group of women at 36-42 weeks of gestation, and in cases of women with early-onset (before 32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia. RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had a three times higher median plasma sFlt1 level than late controls (P<.001). Women with early-onset preeclampsia had a 21 times lower median plasma PlGF level than early controls (P<.001). Women with late-onset preeclampsia had a five times lower median plasma PlGF level than late controls (P=.01). The median level of VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women. CONCLUSION: Both early- and late-onset preeclampsia are associated with altered plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early-onset rather than in late-onset disease.     

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

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

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

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

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

Irisin as an early marker for predicting gestational diabetes mellitus: a prospective study

Objective: The objective of this study is to evaluate maternal serum irisin levels in the first and second trimesters of pregnancy in women diagnosed with and without gestational diabetes mellitus (GDM).

Methods: We performed a prospective, nested case–control study in 258 pregnant women who were enrolled at the time of the first prenatal visit (6–11th weeks of gestation) and followed until delivery. Among the entire population, we selected 20 women who subsequently developed GDM and 30 women with uneventful pregnancies. Blood samples were collected once from each participant at 6–11th weeks of gestation during the fetal viability scan and at 24–28th weeks of gestation during screening for GDM.

Results: In the first trimester, irisin levels were significantly lower in women who later developed GDM (median?=?453?ng/mL, range: 257–811?ng/mL) than in controls (median?=?721?ng/mL, range: 700–786?ng/mL). In the second trimester, the difference in irisin levels between the GDM group (median?=?749?ng/mL; range: 456–910?ng/mL) and controls (median?=?757?ng/mL; range: 703–898?ng/mL) was not statistically significant.

Conclusions: Irisin may be a useful biomarker in early pregnancy to predict the development of GDM.     

Elevated placenta growth factor levels in the early second-trimester amniotic fluid are associated with preterm delivery

Objective: The purpose of this study was to determine how angiogenesis-related factors correlate with preterm delivery.

Methods: A cohort of 382 pregnant women undergoing early second-trimester genetic amniocentesis was enrolled and followed-up until delivery, and the amniotic fluid was collected and stored as a nested case-control study. Cases with preterm delivery (n?=?31) were compared with matched controls with term delivery (n?=?62). The amniotic fluid concentrations of placenta growth factor (PlGF), angiogenins, angiopoietin-2, soluble fms-like tyrosine kinase and soluble endoglin were determined using enzyme-linked immunosorbent assays.

Results: Women who delivered preterm had a higher amniotic PlGF concentration compared with the control group (median 12.6 pg/ml versus 6.1 pg/ml; p=0.027). Other angiogenesis-related factors did not show any differences between case and control groups. The odds ratio for preterm delivery based on amniotic fluid PlGF was 1.031 (95% confidence interval: 1.002–1.061; p=0.035). Additionally, when the cases were subdivided into early preterm, late preterm and term groups, PlGF values between the early preterm and term delivery groups were significantly different (median 16.6 pg/ml versus 6.1 pg/ml; Bonferroni-adjusted p=0.018).

Conclusion: Amniotic fluid PlGF levels in the early second trimester of pregnancy are associated with preterm delivery.     

Magnesium sulphate can prolong pregnancy in patients with severe early-onset preeclampsia

Objective: To assess whether long-term use of magnesium sulphate prolongs pregnancy in patients with severe early-onset preeclampsia.

Methods: Retrospective cohort study included all singleton pregnancies with severe early-onset preeclampsia, expectantly managed in our institution between 2005 and 2013. Obstetric and perinatal outcomes were compared between patients managed using a current protocol that tolerates long-term (over 48 h) use of magnesium sulphate (long-term group, n?=?26) and a historical control group (control group, n?=?15) that underwent conventional treatment (up to 48 h use of magnesium sulphate).

Results: Long-term group showed significant prolongation of pregnancy compared with the control group (9.2?±?7.9 versus 16.6?±?9.3 d, log-rank test, p?=?0.021), which was also observed in patients with severe preeclampsia occurring before 28 weeks’ gestation (n?=?11, 4.5?±?5.2 versus 13.2?±?6.8 d, log-rank test, p?=?0.035). In contrast to a progressive decrease of platelet count in patients managed without magnesium sulphate, administration of magnesium sulphate for 7 d prevented the decrease of platelet count (p?=?0.001). Thirty two percent of patients (13/41) experienced a major complication irrespective of duration of magnesium sulphate use.

Conclusions: Long-term use of magnesium sulphate prolonged pregnancy in patients with severe early-onset preeclampsia and can help alleviate progression of preeclampsia.     

Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre-eclamptic pregnancies

Objective: PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on their expression in the fetal compartment have been reported so far. Study Design: An observational study was performed by prospectively collecting maternal and fetal serum samples in 51 singleton pregnancies divided into two groups: 22 PE women and 29 healthy controls. The relationships between maternal and fetal marker serum levels were evaluated by Spearman correlation. Results: A feto-maternal correlation was neither identified for PTX3 in either PE or control groups (1.1 versus 3.8?ng/ml, p?=?0.17 and 0.9 versus 1.3?ng/ml, p?=?0.30, respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus 3326.0?pg/ml, p?=?0.28 and 11.0 versus 230.9?pg/ml, p?=?0.51). In contrast, PE patients showed a significant positive feto-maternal correlation for both sFlt-1 and PlGF (324.1 versus 10?825.0?pg/ml and 7.8 versus 31.6?pg/ml, respectively, p?=?0.02 for both markers). Conclusion: According to our results, an independent fetal production of the analyzed soluble angiogenic markers can be hypothesized in pregnancies complicated by PE.     

Association of NT-proBNP with plasma renin activity and plasma aldosterone concentration in women with singleton pregnancy

ObjectiveTo determine the association of the N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP) levels with plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in singleton pregnancies.DesignSerum NT-proBNP levels, PRA and PAC were determined in 215 blood specimens from 139 women with singleton pregnancies, including 34 and 105 women who did and did not develop hypertensive disorders in pregnancy, respectively. Twenty-five blood specimens were obtained from 25 women who later developed hypertension (systolic BP ⩾ 140 mmHg and/or diastolic BP ⩾ 90 mmHg), but were normotensive at the time of blood sampling.ResultsThe serum NT-proBNP levels [pg/ml, median (range), 32 (5–142)] did not change in normotensive women, but increased significantly to 97 (23–436) after the development of hypertension (D/H). The PRA [ng/ml/h, median (range), 7.1 (1–20)] did not change in normotensive women, but decreased significantly to 1.9 (1–16) after D/H. PAC (pg/ml) increased significantly from 397 (94–1750) to 667 (123–2010) between the 2nd and 3rd trimesters in normotensive women. However, as PAC of hypertensive women did not change significantly before and after D/H, PAC [293 (116–1720)] after D/H was significantly lower than that [667 (123–2010)] of the 3rd trimester in the normotensive women. The serum levels of NT-proBNP were significantly and negatively correlated with both PRA and PAC.ConclusionsThe renin-angiotensin-aldosterone system is suppressed in pregnant women with cardiac conditions associated with higher NT-proBNP levels.     

Could alterations in maternal plasma visfatin concentration participate in the phenotype definition of preeclampsia and SGA?

Objective.?Women with preeclampsia and those who delivered a small-for-gestational-age (SGA) neonate share several mechanisms of disease, including chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either preeclampsia or SGA. Compelling evidence suggests that adipose tissue orchestrates both metabolic pathways and immunological responses via the production of adipokines. Visfatin is a novel adipocytokine with metabolic and immunomodulating properties. The objective of this study was to determine whether preeclampsia and SGA are associated with alterations in maternal circulating visfatin concentrations.

Methods.?This cross-sectional study included pregnant women in the following groups: (1) normal pregnancy (n?=?158); (2) patients with preeclampsia (n?=?43) of which 32 had an AGA and 11 had an SGA neonate; (3) patients without preeclampsia who delivered an SGA neonate (n?=?55). Maternal plasma visfatin concentrations were measured by ELISA. Nonparametric tests and multiple linear regression analysis were used.

Results.?(1) Women who delivered an SGA neonate had a higher median maternal plasma visfatin concentration than those with a normal pregnancy (20.0?ng/ml, interquartile range: 17.2–24.6 vs. 15.2?ng/ml, 12.1–19.2, respectively; P?<?0.001) and than those with preeclampsia (14.5?ng/ml, 12.5–18.7; P?<?0.001); (2) the median maternal plasma visfatin concentration did not differ significantly between patients with preeclampsia and those with a normal pregnancy (P?=?0.8); (3) among patients with preeclampsia, there was no significant difference in the median maternal plasma visfatin concentration between those with or without an SGA neonate (P?=?0.5); (4) in a linear regression model, delivery of an SGA neonate and pregestational body mass index were independently associated with increased visfatin concentration after adjustment for confounding factors (maternal age, smoking, gestational age at blood collection and the presence of preeclampsia or SGA).

Conclusion.?(1) Patients with SGA, but not those with preeclampsia, had a higher maternal plasma visfatin concentration than those with a normal pregnancy; (2) this finding suggests differential involvement of visfatin in SGA and preeclampsia; (3) we propose that changes in circulating maternal visfatin concentration may be implicated in the phenotypic definitions and distinction of preeclampsia and SGA.