Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia

Objective: The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia.

Material and method: This case–control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated.

Results: NGAL and PCT concentrations were significantly higher in preeclamptic group (p?p?=?0.001, respectively) and their levels were correlated with the severity of the preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81–13.21) and higher PCT (OR: 6.67; 95% CI: 2.44–18.21) concentrations had higher risk for preeclampsia.

Conclusion: NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.     

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.     

Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia

Neutrophil gelatinase-associated lipocalin (NGAL) concentrations, a product of neutrophils, were investigated in normal and preeclamptic pregnancies. Prospectively collected data and late second trimester (24-26 weeks) serum samples from 48 women who subsequently developed preeclampsia (PE) and 96 control women with uncomplicated pregnancies were compared. Serum NGAL values, as determined by quantitative sandwich enzyme immunoassay, were significantly increased in the preeclamptic compared to the control women: 76.9 ng/ml (interquartile range 39.7-96.5) versus 16.0 ng/ml (interquartile range 11.2-24.4) (p<0.001), and were positively correlated to blood pressure and proteinuria, showing a high sensitivity (75%) and specificity (94.5%). The results suggest that serum NGAL might be involved in the pathophysiology of PE and could be a marker for this syndrome.     

Magnesium intoxication in women with preeclampsia with severe features treated with magnesium sulfate

ABSTRACT

Objective

To evaluate the maternal-neonatal outcome in magnesium (Mg)-intoxicated women with preeclampsia with severe features (PESF) treated with magnesium sulfate (MgSO₄).     

中性粒细胞明胶酶相关脂质运载蛋白与子痫前期及妊娠期糖尿病孕妇糖代谢和脂代谢指标的相关性

目的 通过测定正常妊娠孕妇、子痫前期糖代谢正常患者、妊娠期糖尿病( gestational diabetes mellitus,GDM)患者及子痫前期合并GDM患者血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平,探讨NGAL与子痫前期、GDM孕妇糖代谢和脂代谢的相关性. 方法 选取2009年12月至2010年11月在广州医学院附属广东省妇女儿童医院定期产前检查并分娩的单胎正常妊娠孕妇、子痫前期糖代谢正常患者及GDM患者各77例,子痫前期合并GDM患者32例.测定所有研究对象血清NGAL、空腹血精、空腹胰岛素、脂代谢参数、尿酸、肌酐、乳酸脱氢酶及24 h尿蛋白等指标,测量血压,计算体重指数(body mass index,BMI),用稳态模型评估法计算胰岛素抵抗指数(homeostasis model assessment for insulin resistance,HOMA-IR)评价胰岛索敏感性.正态分布资料用单因素方差分析及Student's t检验进行比较,非正态分布资料用Kruskal-Wallis H检验和Mann-Whitney U检验进行比较.采用Spearman相关分析和多元逐步回归法进一步分析. 结果 子痫前期合并GDM组孕妇血清NGAL水平高于子痫前期糖代谢正常组[(70.82±20.02) ng/ml与(56.17±18.22)ng/ml,t=3.65,P＜0.01]、GDM组[(43.99±14.82) ng/ml,t=5.97,P＜0.01]及正常妊娠组[(17.80±5.78) ng/ml,t=14.76,P＜0.01);子痫前期糖代谢正常组血清NGAL水平高于GDM组(t=5.90,P＜0.01);子痫前期合并GDM组和子痫前期糖代谢正常组中,子痫前期重度组血清NGAL水平均高于子痫前期轻度组[(76.44±28.06)ng/ml与(60.15±25.86) ng/ml,t=2.82,P＜0.05; (61.61±37.14) ng/ml与(46.30±13.97) ng/ml,t=4.74,P＜0.01].校正孕周、孕妇年龄后血清NGAL水平与孕前BMI(r=0.335,P＜0.01)、入组BMI(r=0.427,P＜0.01)、入组收缩压(r=0.648,P＜0.01),入组舒张压(r=0.664,P＜0.01)、空腹血糖(r=0.320,P＜0.01)、空腹胰岛素(r=0.381,P＜0.01)、HOMA-IR(r=0.399,P＜0.01)、甘油三酯(r=0.405,P＜0.01)、总胆固醇(r=0.145,P＜0.05)、游离脂肪酸(r=0.335,P＜0.01)、尿酸(r=0.292,P＜0.01)、肌酐(r=0.226,P＜0.01)及24 h尿蛋白(r=0.436,P＜0.001)呈正相关,与高密度脂蛋白胆固醇(r=-0.189,P=0.008)呈负相关.多元逐步回归分析显示,入组收缩压(β=0.251,P＜0.01),入组舒张压(β=0.351,P＜0.01)、HOMA-IR(β=0.265,P＜0.01)、24 h尿蛋白(β=0.140,P＜0.05)是血清NGAL的独立相关因素. 结论 子痫前期及GDM患者血清NGAL水平显著升高,与糖脂代谢及血管内皮功能失调相关,提示NGAL可能在子痫前期及GDM的病理生理过程中发挥作用.     

Urinary angiogenic factors cluster hypertensive disorders and identify women with severe preeclampsia

OBJECTIVE: Serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) are altered in women with clinical preeclampsia. We sought to identify whether similar alterations in urinary levels of these proteins cluster hypertensive disorders in pregnancy, and identify women with severe preeclampsia (sPE). STUDY DESIGN: Free urinary levels of sFlt-1, VEGF, and PlGF were measured by immunoassay in 68 women enrolled prospectively in the following groups: nonpregnant reproductive age (NP-CTR n = 14), healthy pregnant control (P-CTR n = 16), pregnant hypertensive and proteinuric women who did not meet criteria for severe preeclampsia (pHTN n = 21), and women with sPE (n = 17). RESULTS: There was no difference in gestational age at the time of enrollment among groups (median [range]: sPE: 31 [24-40], pHTN: 34 [16-40], P-CTR: 28 [7-39] wks). Urinary excretion of VEGF was significantly increased in sPE women compared with NP-CTR (P = .023), but did not differ among pregnant groups. Urinary PlGF levels were significantly increased in pregnant compared with nonpregnant women, but were decreased in all hypertensive women compared with healthy P-CTR (P < .001). Urinary sFlt-1 concentrations were significantly increased in women with sPE relative to all other groups (P < .001). pHTN women had higher sFlt-1 urinary output compared with P-CTR group (P = .001). A cutoff >2.1 in the ratio log [sFlt-1/PlGF] had 88.2% sensitivity and 100% specificity in differentiating women with sPE from normotensive controls. We also described that the log[sFlt-1/PlGF] ratio identified women with sPE better than proteinuria alone (P = .03). Our regression model revealed that uric acid correlated best with log[sFlt-1/PlGF] ratio (r = 0.628; P = .005). CONCLUSION: sPE is associated with increased urinary output of the antiangiogenic factor sFlt-1 and a decreased output of PlGF at the time of clinical manifestation, providing a rapid noninvasive screening of hypertensive women based on a sFlt/PlGF ratio. This ratio may be used as representation for severity of the disease, and appears to be superior to random urinary protein measurements.     

History of abortion and perinatal outcomes associated with preeclampsia in nulliparous Japanese women

The purpose of the present study was to examine the influence of history of abortion on the next pregnancy outcomes associated with preeclampsia. This investigation involved 5206 nulliparous Japanese women with singleton pregnancies who delivered after 22 weeks of gestation. The patients were divided into two groups: those with a history of spontaneous and/or artificial abortion during the previous pregnancies after the marriage with the same partner (n?=?1029) and those without a history of abortion (n?=?4173). There was no significant difference in the incidence of preeclampsia between the 2 groups with and without previous abortions (4.0% vs. 3.9%, p?=?0.91). In addition, there were no significant differences in the incidence of perinatal complications associated with preeclampsia between the 2 groups. Although further studies may be needed, based on the current results history of abortion does not seem to affect perinatal outcomes associated with preeclampsia.     

Reduced circulating miR-196b levels is associated with preeclampsia

MicroRNAs (miRs) are small noncoding RNAs, highly stable in plasma, that regulate gene expression by base-pairing to the 3′-untranslated region of target mRNAs. We compared the expression of 3 circulating miRs (miR-125b, miR-146a, and miR-196b), which is related to the control of cell proliferation, differentiation, and apoptosis in preeclamptic (n = 19) and healthy pregnant women (n = 14). We found that women with preeclampsia (PE) presented lower expression of miR-196b (−2.9-fold change). The other miRs were at similar levels. This study is the first to demonstrate this difference, and highlights new opportunities for investigation into the role of miRs in PE.     

Physical well-being in women with a history of severe preeclampsia

Objective.?To evaluate the physical and mental health of women with a history of severe preeclampsia.

Methods.?In a historical cohort study 131 former patients with a history of severe preeclampsia and 127 control patients received questionnaires about experienced physical and mental complaints after delivery. At a follow-up visit blood pressure, body mass index, and proteinuria were measured and venous blood was drawn.

Results.?Former patients experienced significantly (p?<?0.001) more frequent problems of headache (31% vs. 2%), right upper quadrant pain (16% vs. 1%), visual disturbances (21% vs. 1%), tiredness (66% vs. 27%), subjective loss of concentration (37% vs. 16%), and mental health (37% vs. 6%) compared with controls. When present, these health problems, except for tiredness, lasted significantly more often beyond six months postpartum compared to controls. Admittance to the intensive care unit was associated with headache, and subjective loss of memory and concentration over a longer period of time. The risk of recurrence of severe preeclampsia was a subject of concern in 20% of former patients. At follow-up, systolic and diastolic blood pressures were significantly higher (p?<?0.001) among former patients.

Conclusion.?Patients with a history of severe preeclampsia more frequently reported physical and mental complaints, also during a longer period of time.     

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.     

妊娠中期孕妇血清中可溶性endoglin水平对重度子痫前期预测的探讨

目的探讨妊娠中期14～20周孕妇血清中可溶性endoglin（sEng）水平是否对重度子痫前期有预测价值。方法前瞻性留取2008年11月至2009年10月妊娠14～20周孕妇行唐氏筛查时的血清,追踪孕妇的妊娠结局,获取早发型重度子痫前期组14例,晚发型重度子痫前期组25例,正常对照组25例和早产组13例,用ELISA方法测定各组孕妇妊娠中期血清中sEng的浓度,数据表示为中位数（四分位数间距）形式。结果早发型重度子痫前期组、晚发型重度子痫前期组、正常对照组和早产组孕妇妊娠中期血清中的sEng浓度分别为0.440ng/ml（0.526ng/ml）、0.594ng/ml（0.457ng/ml）、0.483ng/ml（0.194ng/ml）、0.460ng/ml（0.204ng/ml）。各组孕妇血清中sEng浓度间差异无统计学意义（Chi-Square值=1.371,P=0.712）。结论妊娠中期14～20周孕妇血清中的sEng水平对重度子痫前期尚未显示出明显的预测价值。     

Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom

OBJECTIVE: Because the trace element selenium behaves as an antioxidant and peroxynitrite scavenger when incorporated into selenoproteins, our objective was to determine whether low selenium status was associated with a greater risk of occurrence of preeclampsia. STUDY DESIGN: Fifty-three preeclamptic patients and 53 matched pregnant controls at the John Radcliffe Hospital, Oxford, gave clippings of their toenails (laid down from 3-12 months previously) for selenium determination by neutron activation analysis. Clinical characteristics of the women and their infants were recorded. Statistical analysis was by Wilcoxon signed rank test and odds ratios were calculated by the ratio of discordant pairs. RESULTS: Median toenail selenium concentrations in the preeclamptic subjects were significantly lower than in their matched controls (P=.001). Being in the bottom tertile of toenail selenium was associated with a 4.4-fold (95% CI 1.6-14.9) greater incidence of the condition. Within the preeclamptic group, lower selenium status was significantly associated (P=.029) with more severe expression of disease, as measured by delivery before 32 weeks. CONCLUSION: In the light of the reduction in selenium status in a number of European countries in recent years, this study raises the question of whether a small increase in selenium intake might help prevent preeclampsia in susceptible women.     

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.     

慢性高血压并发早发型重度先兆子痫单胎孕妇围产期母儿结局的回顾性分析

目的探讨慢性高血压并发早发型重度先兆子痫较单纯早发型重度先兆子痫是否会增加母儿的不良结局。方法自1999年7月1日至2009年6月30日北京大学第一医院共收治早发型重度先兆子痫单胎孕妇300例,其中慢性高血压并发早发型重度先兆子痫者59例(A组),单纯早发型重度先兆子痫者241例(B组),对两组孕妇的母儿结局进行分析,讨论慢性高血压并发早发型重度先兆子痫是否会增加母儿的不良结局。结果两组孕妇一般情况没有明显的差异,A组的最高收缩压和舒张压明显高于B组(P0.05)。两组孕妇严重并发症如胎盘早剥、HELLP综合征、肺水肿、肝功能损害和子痫等发生率比较,差异无统计学意义(P0.05)。A组除了新生儿呼吸窘迫综合征的发生率明显高于B组外(P0.05),两组围产儿死亡率、胎儿生长受限、新生儿窒息、颅内出血和坏死性小肠结肠炎的发生率比较,差异无统计学意义(P0.05)。结论在病情允许的情况下,通过严密监测母儿一般状况、积极地对症治疗并采用适当的期待疗法,慢性高血压并发早发型重度先兆子痫较单纯早发型重度先兆子痫没有对母儿造成明显的不良后果。     

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.     

Placental sFLT1 is associated with complement activation and syncytiotrophoblast damage in preeclampsia

The immune complement system protects against pathogens; however, excess activation results in disease like hemolytic uremic syndrome, a clinical imitator of preeclampsia. Vascular endothelial factor (VEGF) protects against aberrant complement activation and is inhibited by soluble fms-like tyrosine kinase-1 (sFLT1) in other organs. We hypothesize that sFLT1 promotes complement-mediated placental damage through VEGF inhibition in preeclampsia.

Objective: Quantify placental complement activity and sFLT1 expression in preeclampsia, and the subgroup of preeclampsia with hemolysis elevated liver enzymes low platelets (HELLP) syndrome.

Methods: Placental complement activation marker C4d, membrane attack complex (MAC), and sFLT1 expression was quantified using immunofluores cence microscopy.

Results: Placentas from 18 controls, 25 preeclampsia, including 6 cases of HELLP syndrome were identified. Placental C4d expression was greater in PE (median 6.4 [IQR: 5.1, 8.3]) compared to controls (4.4 [3.6, 5.5]; p = 0.003). MAC expression was also increased in preeclampsia compared to controls (6.5 [5.8, 8.7]; 5.4 [2.9, 5.9], p = 0.001). Placental sFLT1 expression was also higher in preeclampsia (p <0.0001). C4d and MAC were strongly correlated with sFLT1 levels in the placenta (R = 0.72; p < 0.0001 and R = 0.59; p = 0.01, respectively). Complement and sFLT1 expression was elevated in HELLP compared to preeclampsia without laboratory abnormalities, but this difference did not reach statistical significance.

Conclusion: Increased placental complement activation and damage was seen in preeclampsia and correlates with sFLT1 expression. Our findings support the importance of the complement pathway in preeclampsia.