Urinary neutrophil gelatinase-associated lipocalin is associated with preeclampsia in a cohort of Turkish women

Purpose: We investigated the optimal cut-off level for urinary neutrophil gelatinase-associated lipocalin (NGAL) in preeclamptic patients to confirm the diagnosis.

Methods: Urinary NGAL concentrations were measured by specific enzyme-linked immunosorbent assay (ELISA).

Results: Patients with preeclampsia had significantly higher urinary NGAL concentrations than controls (mean: 387 ng/ml vs. 188 ng/ml, respectively; P< 0.001). Using a cutoff value 252 ng/ml for urinary NGAL to confirm diagnosis of preeclampsia, sensitivity, and specificity were 92% and 91%, respectively.

Conclusion: Urinary NGAL concentrations were significantly elevated in women with preeclampsia versus normotensive controls.     

Second-trimester urinary neutrophil gelatinase-associated lipocalin levels in gestational diabetes: preliminary results

Objective: The objective of this study is to investigate the urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in the second trimester of pregnant patients at the time of gestational diabetes mellitus (GDM) screening.

Materials and methods: Urinary samples from 88 pregnant women who underwent gestational diabetes screening test were collected in late second trimester (24–28 weeks) prospectively. After an overnight fasting, 75?g GTT was performed. The blood samples were drawn for measurement of glucose, insulin, and HbA1c. The urinary and blood parameters were compared for pregnant women with or without gestational diabetes.

Results: uNGAL levels were significantly elevated in pregnant women with gesting compared with the control groups (p?p?=?.001).

Conclusions: In the second trimester, at the time of GDM screening, high levels of uNGAL indicate tubular injury in GDM cases which seems to be a result of hyperglycemia. uNGAL may correlate with an inflammatory renal involvement in GDM.     

Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease

ObjectiveTo investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID).Materials and methodsSixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed.ResultsPlasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery.ConclusionPlasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay.     

Association of serum N-terminal pro-brain natriuretic peptide levels with the severity of preeclampsia

Objective: To investigate whether serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could be used as a marker to determine the severity of preeclampsia.

Methods: This prospective cohort study included pregnant women with preeclampsia and severe preeclampsia and normotensive pregnant controls admitted between January 2013 and July 2014. Preeclampsia was graded according to the recently revised criteria of the American College of Obstetricians and Gynecologists (ACOG). Serum NT-proBNP levels were compared among the groups.

Results: Of the 49 women with preeclampsia, 25 had severe preeclampsia. The controls were 27 normotensive pregnant women admitted during the same period. Serum NT-proBNP levels were significantly higher in the preeclampsia groups than in the control group (p?<?0.001). In addition, NT-proBNP levels were significantly higher in the severe preeclampsia group compared with both the preeclampsia group (p?<?0.001) and the control group (p?<?0.001).

Conclusion: The ACOG has recently revised the grading of hypertensive diseases of pregnancy and the criteria for severe preeclampsia. In line with these revised guidelines, serum NT-proBNP levels appear to be a useful marker to evaluate the severity of preeclampsia.     

Maternal serum glycodelin levels in preeclampsia and its relationship with the severity of the disease

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.

Methods: This is a prospective case–control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.

Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38?±?22.78 versus 42.32?±?12.28?ng/ml, p?p?r?=?0.637 and r?=?0.714, respectively, p?r?=?0.369, p?=?.006 and r?=?0.377, p?=?.005) and proteinuria (r?=?0.342, p?=?.011). Moreover, it was correlated with birth weights and gestational age at delivery (r?=??0.386, p?=?.004 and r?=??0.394, p?=?.003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p?53.64?ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p?83.97?ng/ml.

Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia.     

Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with normal CA125 levels

Objective

To determine whether urinary matrix metalloproteinases (MMPs) predict the presence of ovarian cancer in patients with CA125 levels below the normal threshold of 35 U/mL, a critical group of patients for whom no ovarian cancer biomarker is currently available. To determine whether these noninvasive biomarkers provide clinically useful information in the general ovarian cancer patient population as well.

Methods

ELISA analyses and substrate gel electrophoresis detected the levels and activity of urinary MMP-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex, and MMP-9 dimer in all ovarian cancer patients (n = 97), those with CA125 < 35 U/mL (n = 26) and controls (n = 81).

Results

In patients with CA125 < 35 U/mL, receiver-operating characteristic (ROC) area under curve (AUC) analysis demonstrated that either urinary MMP-2 or MMP-9 or NGAL significantly discriminated between controls and ovarian cancer patients with normal CA125. Multivariate logistic regression revealed that the combination of urinary MMP-2 and MMP-9 provided the best diagnostic accuracy when multiplexed. When further multiplexed with age, the diagnostic accuracy of these biomarkers increased to a significant AUC of 0.820. These findings were consistent among the general ovarian cancer population studied as well, where the combination of urinary MMP-2 and MMP-9 multiplexed with age resulted in a highly significant AUC of 0.881. Pearson chi-square analysis revealed that higher urinary levels of either MMP-2 or MMP-9 were strongly associated with the increasing percentage of women with ovarian cancer independent of CA125 levels.

Conclusion

This study demonstrates the potential utility of urinary MMP-2 and MMP-9 to differentiate between ovarian cancer patients with normal CA125 levels and controls and suggests that urinary MMP-2 and MMP-9 may be a clinically useful aid in the diagnosis of advanced or recurrent ovarian cancer.     

Maternal serum sestrin 2 levels in preeclampsia and their relationship with the severity of the disease

Objective: To investigate sestrin 2 (SESN2) levels in preeclampsia (PE) cases and uncomplicated pregnancies.

Methods: Cross-sectional study including 26 pregnant women with PE, 24 with severe-PE, and 30 randomly selected healthy pregnant women.

Results: The mean arterial pressure, severe proteinuria, number of HELLP syndrome cases, and serum SESN2 levels in the severe PE group were significantly higher than those in the other groups (p < 0.001, p < 0.001, p = 0.006, and p = 0.004, respectively). Negative correlation was found between the birth interval (r = ?.262, p = 0.019) and the SESN2 level.

Conclusion: SESN2 seems to play a role in the pathophysiology of PE, especially in severe PE cases.     

The reduction of melatonin levels is associated with the development of preeclampsia: a meta-analysis

Objective: The aim of this analysis was to demonstrate the association between melatonin levels and the development of preeclampsia.

Methods: Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using a random effects model.

Results: The pooled SMD between case and control was 1.40 (95% CI: 0.26, 2.55; P = 0.02). And the pooled SMD between mild PE and severe PE was 5.25 (95% CI: 1.5, 9.01; P = 0.006).

Conclusion: The meta-analysis illustrated that melatonin concentration was significantly lower in women with preeclampsia, and correlated with the severity of the disease.     

Endogenous inhibitors of nitric oxide and preeclampsia: A review

Nitric oxide (NO) is a potent vasodilator. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia.     

Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in nulliparous women complicated with preeclampsia

Objective: To determine the prevalence of C677T and A1298C Single-nucleotide polymorphisms (SNPs) of the MTHFR gene in nulliparous women complicated with preeclampsia (PE).

Methods: One hundred fifty gestations complicated with PE and their corresponding controls without the disease were recruited for the genotyping of C677T and A1298C polymorphisms of the MTHFR gene using restriction fragment length polymorphism polymerase chain reaction. Secondarily, homocysteine (HCy) plasma levels were measured in preeclamptic women displaying the CC genotype of the A1298C polymorphism (homozygous) and compared to HCy levels determined among controls with the normal AA genotype for the A1298C variant.

Results: Only the mutant CC genotype of the A1298C polymorphism was associated to higher risk of presenting PE, as frequency of this genotype was significantly higher among cases than controls (15.3% versus 0.7%, p?p?=?0.0001). Women with the mutant CC A1298C SNP displayed higher plasma HCy levels as compared to controls with normal AA A1298C genotype (8.4?±?2.6 versus 7.5?±?2.7?mmoL/L p?=?0.04).

Conclusion: Prevalence of the CC mutant genotype of the A1298C polymorphism was higher among PE women. This mutation among PE women was related to increased neck circumference and higher HCy levels. Future research should aim at linking these gestational findings with obesity and cardiovascular risk.     

Evaluation of the effects of fasting associated dehydration on maternal NGAL levels and fetal renal artery Doppler parameters

Objective: The aim of this study was to evaluate maternal neutrophil gelatinase-asssociated lipocalin (NGAL) levels and fetal renal artery (fRA) Doppler flow indices in pregnant women fasting in Ramadan in respect of dehydration in long hot summer days as a marker of hypoperfusion and early renal injury.

Methods: A cross-sectional observational study was carried out at a University Hospital. Fasting pregnant women and non-fasting age, gravidity and gestational age-matched women were evaluated for hematologic, blood biochemistry and urine parameters in the first and fourth weeks of the Ramadan. Umbilical artery and fRA Doppler flows were studied in each evaluation.

Results: Blood urea nitrogen, potassium and hematocrit levels, blood and urine NGAL levels were significantly higher, and fRA Doppler indices increased in fasting women (p?<?0.05) during the second visit in the last week of the Ramadan, while non-fasting women had no significant alterations in each evaluation (p?>?0.05).

Conclusions: Adequate maternal vascular volume is essential for the maintenance of healthy pregnancy. Fasting during the long and hot summer days leads to fluid deprivation and dehydration which was found to be related to subclinical maternal renal dysfunction and increased fRA Doppler indices.     

Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in the placenta of pregnancies complicated with preeclampsia

Abstract

Background: Preeclampsia has been related to single-nucleotide polymorphisms (SNPs) of the methylenetetrahydrofolate reductase (MTHFR) gene; however, data regarding the placenta are still lacking.

Objective: To determine the frequency of C677T and A1298C SNPs of the MTHFR gene in the placenta of preeclamptic pregnancies and healthy controls.

Methods: Genotyping of C677T and A1298C polymorphisms of the MTHFR gene using RFLP-PCR was performed to the placenta of 100 gestations (n?=?50 complicated with preeclampsia and n?=?50 normal controls matched for parity and maternal age).

Results: Gestational age at birth and neonatal and placental weight were significantly lower in women with preeclampsia as compared to controls. The TT genotype of the C677T polymorphism was threefold more prevalent in preeclamptic placentas as compared to the placenta of controls (24.0% versus 8.0%, p?=?0.001). Upon pooled analysis (n?=?100), placental and neonatal weights were significantly lower in placentas displaying this genotype (TT, C677T) as compared with the CC genotype.

Conclusion: This study found that the frequency of the TT mutant genotype of the C677T polymorphism was higher in the placenta of pregnancies complicated with preeclampsia. There is a need for further research in this matter.     

Correlations of maternal neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight

Objective: The aim of this study is to investigate the possible correlation of hemogram parameters including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with birth weight and gestational week.

Materials and methods: This prospective study has been conducted with 783 patients. The maternal age, parity, gestational age, type of delivery, values of complete blood count (CBC) variables and the weight of newborn were recorded. We analyzed the statistical differences between the NLR, PLR, hemoglobin (HGB), platelet distribution width (PDW), red cell distribution width (RDW), mean platelet volume (MPV), platelet, neutrophil, lymphocyte and white blood cells (WBC) in terms of the birth weight.

Results: There was no statistically significant difference in the NLR in terms of the birth weight (p?=?0.097), whereas there was a statistically significant difference in the PLR (p?p?=?0.011 and p?Conclusion: This prospective study is the first in the literature which investigates the correlation of NLR and PLR with the week of birth and birth weight of the infant. Our study suggested that the maternal NLR and PLR are negatively correlated with the week of birth and birth weight of the infant.     

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.     

MIF和子痫前期炎症反应机制的关系

目的研究子痫前期胎盘组织炎症反应情况及巨噬细胞移动抑制因子（MIF）的表达,探讨MIF在子痫前期炎症反应中的作用。方法选取住院分娩的子痫前期孕产妇53例,其中轻度子痫前期孕产妇25例（轻度子痫前期组）,重度子痫前期孕产妇28例（重度子痫前期组）。另选取同期正常妊娠晚期孕产妇30例为对照组。采用逆转录（RT）PCR技术检测三组孕产妇胎盘组织中MIFmRNA的表达;采用免疫比浊法检测三组孕产妇血浆中CRP水平;采用ELISA方法检测三组孕产妇血浆中（TNF-α）、IL-6浓度。并对轻度及重度子痫前期组孕产妇血浆中CRP水平与胎盘组织中MIFmRNA表达的相关性进行分析。结果①三组孕产妇胎盘组织中均有MIF的表达,轻度子痫前期组孕产妇胎盘组织中MIFmRNA的水平为（0.84±0.13）,重度子痫前期组为（1.05±0.11）,两组比较,差异有统计学意义（P〈0.01）。对照组孕产妇胎盘组织中MIFmRNA为（0.70±0.12）,明显低于轻度及重度子痫前期组,差异均有统计学意义（P〈0.01）;②轻度子痫前期组孕产妇血浆CRP、（TNF-α）、IL-6浓度分别为（14.99±6.85）mg/L、（14.76±3.67）pg/ml、（24.68±10.13）pg/L,重度子痫前期组孕产妇血浆CRP、（TNF）、IL-6浓度分别为（21.16±8.89）mg/L、（19.66±6.13）pg/ml、（30.91±14.34）pg/L,差异有统计学意义（P〈0.01）;对照组孕产妇血浆CRP、（TNF）、IL-6浓度分别为（4.71±1.76）mg/L、（9.94±2.53）pg/ml、（14.14±5.06）pg/L,明显低于轻度及重度子痫前期组,差异有统计学意义（P〈0.01）;③轻度及重度子痫前期组孕产妇血浆中CRP水平与胎盘组织中MIFmRNA表达水平呈正相关（r=0.67,P〈0.01）。结论子痫前期患者胎盘组织中的MIF的过度表达,可上调血浆中炎性标志物CRP的水平,引起血管内皮损伤,从而参与子痫前期的发病。     

The value of the 24-h proteinuria in evaluating the severity of preeclampsia and predicting its adverse maternal outcomes

Background: To identify the 24-h proteinuria value with quantitative analysis and how it correlates with the severity of preeclampsia and subsequent adverse maternal outcomes in the Chinese population. Study design: Eleven hospitals in 10 provinces across China were chosen, in which 1,738 pregnant women complicated by hypertensive disorders of pregnancy (HDP) with the records of 24 h proteinuria were enrolled. They were allocated into four groups: patients with maximal quantified proteinuria < 0.3 g/24 h (Group 1, n = 328); patients with maximal quantified proteinuria ≥ 0.3 g/24 h and < 2.0 g/24 h (Group 2, n = 638); patients with maximal quantified proteinuria ≥ 2.0 g/24 h and < 5.0 g/24 h (Group 3, n = 353); and patients with maximal quantified proteinuria ≥ 5.0 g/24 h (Group 4, n = 419). Logistic regression analysis were conducted to assess the differences in maternal outcomes between different subgroups of 24-h proteinuria and to identify independent risk factors of adverse maternal outcomes in preeclampsia. The multivariable risk prediction model of adverse maternal outcome for HDP was established with receiver operating characteristic curve (ROC) curve and its predicted value was assessed. Results: Thrombocytopenia and cerebral or visual symptoms were more frequent in Groups 3 and 4 than Groups 1 and 2 but no differences were found between Groups 3 and 4 or Groups 1 and 2. Maternal complications were more frequent in Groups 3 and 4 than in Groups 1 and 2 [Group 3 vs. Group 1, odds ratios (ORs) = 3.359 (1.067–10.571); Group 4 vs. Group 1, OR = 3.628 (1.189–11.086); Group 3 vs. Group 2, OR = 2.845 (1.155–7.003); Group 4 vs. Group 2, OR = 3.082 (1.304–7.288)]. However, no significant difference was found between Groups 4 and 3 or between Groups 2 and 1. The proteinuria ≥ 2 g/24 h had an area under the receiver operating characteristic curve (AUC ROC) of 0.668 (95% confidence interval (CI) 0.632–0.705) for predicting adverse maternal outcome. After adjusting for the effects of other symptoms, signs, and laboratory tests, it was the independent risk factor and predictor factor of the adverse maternal outcome (OR = 3.683, 95% CI 2.439–5.562, P<0.001). The final risk prediction model had an AUC ROC of 0.800 (95% CI 0.769–0.830, P<0.001). Conclusion: The proteinuria ≥ 2 g/24 h is an independent predictive factor of adverse maternal outcomes in preeclampsia, but its individual predictive value is limited. The risk prediction model is effective in assessing the risk of adverse maternal outcomes in patients with HDP.     

Identification of patients at risk for preeclampsia with the use of uterine artery Doppler velocimetry and copeptin

Purpose: To investigate the relationship between maternal copeptin levels and uterine artery Doppler examination and progress of preeclampsia.

Materials and methods: A cross-sectional study was designed with women those were screened at 20?+?0 – 24+ 6 weeks’ gestation between May 2014 and August 2014. The obstetric records of all normotensive women were examined. Uterine artery Doppler velocimetry results and serum copeptin levels were measured. The patients were divided into two groups according to normal (n?=?67) and abnormal uterine artery Doppler (n?=?21) findings.

Results: Maternal age was significantly lower in group 1 (n?=?21, 23.9%) than in group 2 (n=?67, 76.1%) (p?p?=?0.002).

Conclusions: Copeptin levels are significantly higher in patients who develop preeclampsia.