Third trimester plasma neurokinin B levels in women with and without preeclampsia

Objective. This study was undertaken to measure neurokinin B (NKB) levels in pregnant women with and without preeclampsia (PE) in the third trimester. The study focused on the Black (sub-Saharan ancestry) and ‘mixed ancestry’ (synonymous with ‘colored’ and denotes an established race group of Khoisan, European, Malay, Malagascan, African, and South Indian ancestry) populations, constituting the majority of inhabitants of the Western Cape Province of South Africa.

Methods. Questionnaires were used to obtain clinical data from pregnant ‘mixed ancestry’ and Black women. Third trimester plasma NKB levels were determined by enzyme-linked immunosorbent assay technique (EIA) in 72 pregnant women with PE and in 94 healthy women. The EIA results were then correlated with clinical data.

Results. The mean NKB concentration in the PE groups (23.5 ng/L for ‘mixed ancestry’ and 15.0 ng/L for Black women) was significantly higher than in the control groups (3.8 ng/L and 4.4 ng/L, respectively; p ≤ 0.001). No significant differences in maternal clinical data were found between the diseased groups.

Conclusions. Using the EIA technique, this study confirms previous reports of elevated NKB levels in the plasma of PE women in the third trimester. Whether increased NKB levels are causative or merely associated with PE remains unknown, as do the causative molecular mechanisms. Future longitudinal studies are certainly needed to further elucidate the predictive value of NKB in PE.     

Altered plasma neurokinin B levels in patients with pre-eclampsia

Objective(s) This study determines the levels of Neurokinin B (NKB) in the plasma of South African coloured pregnant women with and without pre-eclampsia (PE) and correlates these results with clinical data. Additionally, the peptide radioimmunoassay (RIA) and peptide enzyme immunoassay (EIA) methods were compared in the determination of the Neurokinin B levels, using 58 samples from patients with PE. Methods At the Tygerberg Hospital, Cape Town, SA, 43 pregnant women with PE and 62 healthy pregnant women were recruited, and clinical data were gathered using questionnaires; 58 patient samples were tested by both RIA and EIA. Results The comparison of RIA and EIA revealed an r-value of 0.904. The mean NKB concentration in the PE group (23.5 ng/l) was significantly higher than in the control group (3.8 ng/l). Within the PE cohort, two NKB subgroups could be discerned: those with levels <30 ng/l and those with levels >30 ng/l. Conclusion(s) This study, carried out within a distinct population, confirms previous reports of elevated NKB levels in the plasma of pre-eclamptic women in the third trimester, and established the suitability of EIA for determining NKB levels. Whether the altered NKB levels are causative or merely associated with PE still remains to be determined. The split in the two NKB groups (high and low values) needs further evaluation, as does whether NKB could be used as a screening test or as a predictive factor.     

神经激肽B及其受体在子痫前期患者胎盘、脐血管的表达

目的:探讨子痫前期患者胎盘、脐血管中神经激肽B(NKB)及其受体的表达。方法:用免疫组化SP法检测40例子痫前期患者胎盘与脐带组织中NKB及其受体的分布与定位,以20例正常产妇作为对照。通过高清晰度彩色病理图文分析系统进行定量分析。结果:轻、重度子痫前期胎盘组织中,其NKB含量明显高于对照组(P<0.05,P<0.01),神经激肽受体(NKR)含量亦高于对照组(P<0.05,P<0.05)。重度子痫前期组脐静脉NKR含量高于对照组(P<0.05)。结论:NKB及其受体可能参与子痫前期发病机制。     

Relation between serum uric acid and plasma adenosine levels in women with preeclampsia

The aim of this study was to examine the relationship between plasma adenosine and serum uric acid levels in women with preeclampsia. Maternal arterial blood sampling was performed to measure serum uric acid and plasma adenosine levels in 20 pregnant women complicated by preeclampsia and 22 normal pregnant women at 33-38 weeks of gestation. The average plasma adenosine levels were 0.31 +/- 0.12 micromol/l in the normal pregnant group and 0.45 +/- 0.11 micromol/l in the preeclampsia group. The mean serum uric acid level in women with preeclampsia was 5.9 +/- 0.60 mg/dl, significantly higher than in the normal pregnant women (4.4 +/- 0.69 mg/dl). Positive correlations were found between serum uric acid and plasma adenosine levels in both the group with (r(2) = 0.38, p < 0.05) and the group without (r(2) = 0.54, p < 0.05) preeclampsia. There was also a significant correlation between serum uric acid and plasma adenosine levels on the whole (r(2) = 0.59, p < 0.05). Our results suggest that increased adenosine is a contributing source of preeclamptic hyperuricemia.     

Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia

OBJECTIVES: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity. METHODS: Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked immunoassay. Platelet aggregation was induced by the agonist agents adenosine diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich plasma by aggregometry. RESULTS: Plasma concentrations of active TGF-beta(1) were significantly higher in preeclamptic women (10.41+/-2.07ng/mL) compared with normotensive pregnant women (7.01+/-3.29ng/mL). Platelet number and platelet agonist-induced aggregation percent were significantly lower in patients with preeclampsia than in healthy pregnant women. A significant correlation was observed between TGF-beta(1) plasma levels and platelet agonist-induced aggregation percent as between plasma levels of TGF-beta(1) and platelet number in preeclamptic patients. CONCLUSION: The association between impairment in platelet responsiveness and higher levels of TGF-beta(1) in the plasma of patients with preeclampsia suggests that this cytokine may play a role in the pathophysiological events of preeclampsia that are dependent on platelet activation.     

Homocysteine plasma concentration levels for the prediction of preeclampsia in women with chronic hypertension

OBJECTIVE: The purpose of this study was to evaluate prospectively midtrimester homocysteine concentration levels for the prediction of superimposed preeclampsia in women with chronic hypertension. STUDY DESIGN: Between March 1, 2000, and February 1, 2002, pregnancies that were complicated by chronic hypertension that required medication had homocysteine, vitamin B(12), and folate concentrations measured between 16 and 20 weeks of gestation. All women received folate supplementation. An upper limit threshold for increased homocysteine was defined as the mean value plus 2 SDs. RESULTS: Fifty-seven women were enrolled. Mean homocysteine concentration levels were 5.1+/-1.7 micromo/L for the 16 women who had preeclampsia compared with 4.7+/-1.3 micromo/L for the 41 women without preeclampsia (P=.56). Two of 16 women with preeclampsia (13%) had concentration levels that exceeded the 95th percentile (6.9 micromo/L) compared with 2 of 41 women (5%) without preeclampsia (P=.31). The sensitivity and specificity were 13% (95% CI, 1.6-38.3) and 95.1% (95% CI, 83.5-99.4), respectively. CONCLUSION: Second-trimester homocysteine concentration levels were not helpful in the prediction of preeclampsia in chronically hypertensive women.     

Serum homocysteine levels in pregnant women with preeclampsia

Preeclampsia is one of the most common and severe pregnancy complications, which ethiology remains unclear. It is certain that endothelial dysfunction plays a key role in the development of preeclampsia. Homocysteine is an important independent cardiovascular risk factor, which might induce the endothelial dysfunction observed in preeclampsia. 26 pregnant women--14 with preeclampsia (group 1) and 12 healthy term pregnant controls (group 2) were enrolled in the study between December 2003 and August 2004. Six of the women in this group had a superimposed preeclampsia. The mean homocysteine level in the first group was 11,04 mol/l, while in the control group it was 6,24 micromol/l (p < 0.05). The women with a severe preeclampsia had a significantly higher serum homocysteine levels than those with mild form (F = 0.025). Seven of the patients (50%) gave birth before 34th weeks of gestation. The study finds a link between the serum homocysteine as an endothelial dysfunction marker and the development of preeclampsia and a relation between the severity of preeclampsia and the degree of the elevation of the serum homocysteine levels.     

Cervicovaginal fetal fibronectin levels in women with preeclampsia

OBJECTIVE: To estimate the mean levels of fetal fibronectin in cervicovaginal secretions of women with preeclampsia and compare them with levels in normotensive controls. METHODS: Cervicovaginal swabs were obtained before digital examination from women who presented to labor and delivery for evaluation of preeclampsia and compared with fetal fibronectin levels from a group of control subjects with a similar gestational age. Fetal fibronectin was assayed by a specific enzyme-linked immunoassay. A concentration greater than 50 ng/mL was considered a positive result. RESULTS: Forty women with preeclampsia (17 mild and 23 severe) and 31 normotensive women were analyzed. The control group had 9.7% positive fetal fibronectins, whereas the preeclampsia group had 15% positive, P =.72, with 80% power to detect a 22% difference. The majority of the quantitative values in both groups were less than 20 ng/mL. There was not a significant difference between the two groups in quantitative cervicovaginal fetal fibronectin, P =.72, nor was there a difference between the women with severe preeclampsia and the controls, P = 1.0, or between the nulliparous women with preeclampsia versus the nulliparous controls, P =.3. CONCLUSION: Fetal fibronectin is not elevated in cervicovaginal secretions of women with preeclampsia.     

Androgen levels in the third trimester of pregnancy in patients with preeclampsia

OBJECTIVE(S): To investigate if testosterone levels are higher in patients with preeclampsia compared to normotensive pregnant patients. STUDY DESIGN: The levels of serum total and free testosterone, dehydroepiandrosterone sulfate, androstenedione and sex hormone binding globulin were estimated in 28 patients during the third trimester of pregnancy with established preeclampsia and 25 normotensive women. RESULTS: No statistically significant differences were noted between the two groups regarding the maternal age, gestational age, body mass index (BMI) haematocrit and neonatal sex. The mean+/-S.D. total testosterone and free testosterone levels were significantly higher (p < 0.01) in the group with preeclapsia compared to the control group. The values of DHEA-S, androstenedione and sex hormone binding globulin were lower in the group with preeclampsia but the difference did not reach statistical significance. CONCLUSION(S): The levels of total and free testosterone appear to be higher in patients with preeclampsia compared to normotensive pregnant women during the third trimester of pregnancy. This difference could indicate an involvement of testosterone in the pathophysiology of preeclampsia and stimulates research in the potential role of anti-androgens in the management of preeclampsia.     

Interleukin-18 in the plasma of women with preeclampsia

OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine capable of stimulating interferon gamma and tumor necrosis factor-alpha production. Our purpose was to determine whether abnormal levels of IL-18 in maternal plasma correlate with the diagnosis of preeclampsia. STUDY DESIGN: A case control study design was used to enroll 61 patients: controls (n = 31) and preeclamptic women (n = 30). A standard enzyme-linked immunosorbent assay measured plasma IL-18. Statistical methods included Student t tests and chi(2) tests. RESULTS: Mean IL-18 levels were lower in preeclampsia than in controls (185 +/- 74 pg/mL vs 224 +/- 75 pg/mL, P =.053). Administration of betamethasone (BMZ) and/or hydralazine (HYD) was significantly associated with a lower IL-18 compared with controls (159 +/- 50 pg/mL vs 224 +/- 75 pg/mL, P =.002). After women who received BMZ or HYD were excluded, levels of IL-18 in preeclampsia were similar to those of controls (213 +/- 87 pg/mL, P =.69). There was no association between gestational age and IL-18. CONCLUSION: Lower IL-18 was associated with administration of either BMZ or HYD. After patients receiving these medications were excluded, IL-18 levels were similar in controls and preeclamptic women. IL-18 was not associated with gestational age.     

Low plasma levels of decoy receptor 3 (DcR3) in the third trimester of pregnancy with preeclampsia

ObjectiveThe pathophysiology of preeclampsia, a major threat during pregnancy characterized by excessive inflammatory status, remains unclear. Decoy receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor (TNFR) superfamily, is capable of inducing anti-apoptosis via binding with TL1A and anti-inflammation by driving Th2 immune reactions. DcR3 may, therefore, play a role in immune modulation during pregnancy. The purpose of this study is to explore the role of DcR3 in normal and preeclamptic pregnancies.Materials and methodsPlasma samples from 104 normal pregnant women (26, 42, and 36 in the first, second, and third trimester, respectively) and 10 patients with preeclampsia in the third trimester were collected. Plasma DcR3 levels were determined by using commercial ELISA kits. ANOVA and linear regression analysis were performed to analyze the relationship between gestational age and DcR3 levels. After adjusting for gestational days, the levels of plasma DcR3 in preeclamptic and non-preeclamptic women in the third trimester were compared.ResultsThe plasma levels of DcR3 gradually decreased as the gestational days increased during pregnancy (p < 0.05). In the third trimester, pregnant women with preeclampsia had significantly lower plasma DcR3 levels compared to non-preeclamptic women (p < 0.05).ConclusionsWe found that plasma DcR3 levels gradually decreased as gestation progressed. The levels of plasma DcR3 in preeclamptic women were significantly lower than those of normal pregnant women, suggesting that a potential involvement of DcR3 in normal pregnancy and decreased levels of DcR3 may be related to preeclampsia.     

Early second-trimester plasma levels of NT-proBNP in women who subsequently develop early-onset preeclampsia

Plasma levels of NT-proBNP are elevated in women with preeclampsia at the time of diagnosis. The objective of this case-control study was to evaluate N-terminal proBNP (NT-proBNP) in maternal plasma as an early second-trimester biomarker for prediction of early-onset preeclampsia. In early second-trimester samples, women who later developed preeclampsia at gestational age 34 wk?+?0 or earlier (n?=?16) had similar plasma levels of NT-proBNP (median 51.8, range 26.1–131.9?pg/ml) as women with uncomplicated pregnancy outcomes (n?=?43) (53.0, 14.9–184.2?pg/ml). The early second-trimester level of NT-proBNP cannot therefore be used as a predictive biomarker of early-onset preeclampsia.     

C-Type natriuretic peptide levels in women with gestational hypertension and preeclampsia

Objective: To measure plasma levels of C-type natriuretic peptide in women with normal pregnancies and those complicated by gestational hypertension and preeclampsia.Methods: We collected venous plasma samples from 20 women with normal pregnancies, 15 with gestational hypertension, and nine with preeclampsia. Gestational ages ranged from 26–39 weeks. We measured C-type natriuretic peptide concentrations by radioimmunoassay. Statistical comparisons were made by one-way analysis of variance and Tukey test.Results: The mean plasma concentration of C-type natriuretic peptide in the women with normal pregnancy was 7.1 ± 2.5 pg/mL, in those with gestational hypertension 9.6 ± 4.2 pg/mL, and in those with preeclampsia 8.1 ± 2.4 pg/mL. There were no statistically significant differences between groups. The statistical power to detect a difference of 3 pg/mL at the 5% significance level was 78% for the group with gestational hypertension and 64% for the preeclamptic group.Conclusion: Our results suggest that C-type natriuretic peptide plasma levels are not significantly different in normal pregnancies and those complicated by gestational hypertension or preeclampsia. In hypertensive pregnancy disorders, C-type natriuretic peptide showed a distinct course compared with atrial natriuretic peptide and brain natriuretic peptide.     

Midtrimester triple test levels in women with severe preeclampsia and HELLP syndrome

BACKGROUND: The levels of midtrimester triple test constituents are known to be altered in hypertensive disorders of pregnancy. OBJECTIVE: Our aim was to determine whether midtrimester triple test constituent levels differ in women with severe preeclampsia and those who also develop HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. METHODS: A retrospective chart analysis of 106 women with severe preeclampsia for whom midtrimester triple test data were available was made. None of these patients had fetuses with abnormal karyotype, nor did they deliver infants with malformations. The levels of midtrimester maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (MShCG) and unconjugated estriol (MSuE3) of 74 patients with severe preeclampsia were compared with those of 32 patients who also developed HELLP syndrome. RESULTS: The mean MShCG was significantly higher and the mean MSuE3 was significantly lower in patients with HELLP syndrome than in those with only severe preeclampsia [1.78 multiple of the medians (MoM), standard error (SE) 0.18 vs. 1.27 MoM, SE 0.07, p=0.015 and 0.86 MoM, SE 0.05 vs. 1.04 MoM, SE 0.07; p = 0.03, respectively]. The two groups did not differ significantly with regard to MSAFP levels. CONCLUSION: Unexplained high levels of midtrimester MShCG and low levels of MSuE3 may be associated with the development of HELLP syndrome in women with severe preeclampsia.     

Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia

Purpose

Preeclampsia (PE) is a specific syndrome of pregnancy clinically identified by hypertension and proteinuria from the 20th week of gestation associated with a systemic inflammatory response and oxidative stress. While pro-inflammatory cytokines have been extensively studied in PE, other factors in the circulation that also influence the magnitude of inflammation have received much less attention. The present study compared serum concentrations of five immune-regulatory compounds in normotensive pregnant women and in women with gestational hypertension (GH) or PE.

Methods

Sixty women with PE, 53 with GH and 40 normotensive women paired by gestational age were evaluated. Sera were evaluated for concentrations of extracellular matrix metalloproteinase inducer (EMMPRIN), hyaluronan, gelsolin, visfatin and histone 2B by ELISA. Differences between groups were analyzed by nonparametric tests, with a significance level of 5 %.

Results

Increased levels of EMMPRIN and hyaluronan were present in preeclamptic women as compared to the GH and normotensive groups. There was no difference between groups in gelsolin, visfatin or histone 2B.

Conclusion

Increased release of EMMPRIN and hyaluronan may contribute to an elevated pro-inflammatory response and tissue damage in women with PE.     

MMP-2 levels are elevated in the plasma of women who subsequently develop preeclampsia.

OBJECTIVE: To determine levels of matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in the plasma of women destined to develop preeclampsia prior to the onset of clinical disease. STUDY DESIGN: Plasma samples were taken from women whose pregnancies were subsequently complicated by preeclampsia and from normal pregnant women at 22 and 26 weeks and at delivery or diagnosis. Following equal protein loading, MMP-2 and 9 and TIMP-1 and 2 were quantified using zymography and Western blot analysis, respectively. RESULTS: Plasma MMP-2 levels were significantly elevated at 22 weeks (p = 0.02) and at diagnosis (p = 0.003) in the preeclampsia group, but there was no difference at 26 weeks. TIMP-1 levels were significantly reduced in the preeclampsia group at 26 weeks (p = 0.0002), but TIMP-2 levels were not quantifiable. CONCLUSION: At all three gestational time points an imbalance in the MMP-2:TIMP-1 ratio was found in patients who subsequently developed preeclampsia. We speculate that increased net MMP-2 activity may contribute to the endothelial dysfunction that is central to the pathophysiology of preeclampsia.     

Serum neopterin levels in women with preeclampsia: a systematic review

ABSTRACT

Objective: Neopterin is a pteridine that is produced following activation of human macrophages upon stimulation with the cytokine interferon-gamma. Several studies suggest its association with preeclampsia and the purpose of the present study is to evaluate this assumption. Methods: We searched the Medline (1992–2018), Scopus (1993–2018) and Google Scholar (1993–2018) databases. All articles that evaluated serum neopterin levels in patients with preeclampsia were held eligible for inclusion, regardless of the trimester of pregnancy in which the measurement was performed. Case reports, animal studies and previous reviews were excluded. Results: A total of 10 studies were finally included in the present review, with a total number of 3,529 pregnant women. Among them 446 were diagnosed with preeclampsia. The majority of included studies reported that serum neopterin was significantly higher in patients with preeclampsia, compared to normotensive pregnant women (p < .05). One study reported that serum levels seem to correlate with the severity of the disease; as patients with HELLP had significantly higher values of neopterin compared to patients with mild and severe preeclampsia. None of the included studies proposed a cut-off value that would help assess the predictive accuracy of this protein for the detection of preeclampsia. Conclusion: Although current data seem to be promising, neopterin remains far from being used in current clinical practice as a biomarker that would help predict and follow-up patients that develop preeclampsia. Future studies are needed, to determine the optimal timing for its measurement and to propose potential cut-off values that would help in this direction.     

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.