Increased secretory sphingomyelinase activity in the first trimester of pregnancy in women later developing preeclampsia: a nested case-control study

2016 ◽  
Vol 397 (3) ◽  
pp. 269-279 ◽  
Author(s):  
Víctor Rodríguez-Sureda ◽  
Francesca Crovetto ◽  
Stefania Triunfo ◽  
Olga Sánchez ◽  
Fátima Crispi ◽  
...  

Abstract The pathogenic basis of abnormal placentation and dysfunction in preeclampsia (PE) is highly complex and incompletely understood. Secretory sphyngomyelinase activity (S-ASM) was analyzed in plasma samples from 158 pregnant women developing PE and 112 healthy pregnant controls. Serum PlGF, sFlt-1, s-Endoglin and sVCAM were measured. Results showed S-ASM activity to be higher in women who later developed PE than in those with uncomplicated pregnancies (40.6% and 28.8% higher in the late- and early-onset groups, respectively). Plasma S-ASM activity correlated significantly with circulating markers of endothelial damage in the late-PE group (endoglin and sVCAM-1), with plasma cholesterol and total lipid levels. However, these significant associations were not observed in the early-PE or control groups. This work provides the first evidence of significantly elevated circulating S-ASM activity in the first trimester of pregnancy in women who go on to develop PE; thus, it may be deduced that the circulating form of ASM is biologically active in PE and could contribute to promoting endothelial dysfunction and cardiovascular programming. Plasma S-ASM measurement may have clinical relevance as a further potential biomarker contributing to the earliest identification of women at risk of developing preeclampsia.

Author(s):  
Rachna Agarwal ◽  
Shweta Chaudhary ◽  
Rajarshi Kar ◽  
Gita Radhakrishnan ◽  
Richa Sharma

Background: We studied the correlation of serum PLGF levels at 11-14 weeks in primigravida for prediction of future preeclampsia in a prospective nested case control study and estimated the critical levels of PLGF for possible use as screening test.Methods: Subjects with preeclampsia/gestational hypertension were taken as cases with an equal number of controls.Results: Out of 300 participants, final analysis was possible in 291 subjects. Thirty five were cases; two had early PE, 15 late PE and 18 had GH. PLGF level was lower in cases (20 pg/ml) compared to controls (79 pg/ml). PLGF was significantly lower in PE cases (15 pg/ml) compared to GH cases (34 pg/ml). PLGF had maximum area under the ROC curve (AUC) for PE with value of 0.867. Further, late PE had more AUC (0.853) as compared to GH (0.759). The cut off value for prediction of PE was found to be <30 pg/ml with 88.2% sensitivity and 71.4% specificity.Conclusions: PLGF levels were significantly lower in first trimester serum samples of subjects who later developed either preeclampsia or gestational hypertension. PLGF had better detection rate for PE and late PE as compared to GH.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Liyan Huang ◽  
Li Shang ◽  
Wenfang Yang ◽  
Danyang Li ◽  
Cuifang Qi ◽  
...  

Abstract Background There was a wider disparity in the diet characterization among most studies on diet and pregnancy outcomes in different countries, and the research in northern China is limited. Therefore, the purpose of the present study that was conducted in northwest China was to understand the dietary characteristics of periconceptional women and to explore the relationship between and specific dietary patterns with adverse pregnancy outcomes. Methods A nested case-control study was conducted from October 2017 to November 2018 in Shaanxi, China. Based on a prospective cohort of 368 women who were pregnant or prepared for pregnancy, 63 participants who developed the outcomes of gestational hypertension, gestational diabetes, preterm birth, low birth weight, and birth defects were included in the case group. A total of 237 healthy pregnant women were included during the same period in the control group. Dietary intake was assessed using a validated food frequency questionnaire for the three months before pregnancy and the first trimester. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Dietary patterns were derived using factor analysis. Stratified analysis was performed on the overall, single and multiple adverse pregnancy outcomes categories. Adjustment was made for sociodemographic characteristics and nutritional supplement status. Results Six major dietary patterns were identified. The ‘starchy’ dietary pattern, composed of high intake in noodle and flour products and/or rice and its products, was associated with the odds of developing of adverse pregnancy outcomes (OR: 2.324, 95% CI: 1.293–4.178). This risk remained significant following adjustment for potential confounders of maternal demographic characteristics and nutritional status (aOR: 2.337, 95% CI:1.253–4.331). Strong association were found during the first trimester of pregnancy, but showed no association during the three months before pregnancy (aOR:1.473, 95% CI: 0.682–3.234). Conclusions High starchy food intake was associated with adverse pregnancy outcomes, particularly during the first trimester of pregnancy. Health education focusing on periconceptional dietary patterns could be a practical strategy for preventing adverse pregnancy outcomes.


2018 ◽  
Vol 7 (4) ◽  
pp. 467-470
Author(s):  
Wasan Wajdi Ibrahim ◽  
Afraa Mahjoob Al-Naddawi ◽  
Hayder A. Fawzi

Objectives: Assessment of glycodelin (GD) as a marker for unruptured ectopic pregnancy (EP) in the first trimester of pregnancy. Materials and Methods: This case-control study was conducted during June 2016 to May 2017 in the Obstetrics and Gynecological Department of Baghdad University at Baghdad teaching hospital/medical city complex. In this study, 100 pregnant women in their first trimester of pregnancy were included after clinical and ultrasonic findings. Results: Based on the results, GD levels in EP were significantly lower than those with normal intrauterine pregnancy (1.58 ± 1.18 vs. 30.1 ± 11.9). In addition, using receiver operator curve analysis, the cut-off GD level of 9.5 and less had acceptable validity results (100% sensitivity, 100% specificity, 95% positive predictive value, 100% negative predictive value, and accuracy 100%) to predict EP. Conclusions: In general, serum GD is considered as an excellent predictor of unruptured EP.


2021 ◽  
Author(s):  
Xiaolei Wang ◽  
Jin Huang ◽  
Sisi Long ◽  
Huijun Lin ◽  
Na Zhang ◽  
...  

Abstract Introduction: Genome-wide DNA methylation profiling has been used to identify CpG sites relevant to gestational diabetes mellitus (GDM). However, these sites have not been verified in larger samples. Here, our aim was to evaluate the changes in target CpG sites in the peripheral blood of pregnant women with GDM in their first trimester. Research Design and Methods: This nested case-control study examined a large cohort of women with GDM in early pregnancy (10–15 weeks; n = 80). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites located in 27 target genes were determined using MethylTarget™ sequencing. The best cut-off levels for methylation of CpG sites were determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Results Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at 7 CpG sites were significantly lower (P < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for GDM prediction. After adjusting for possible confounders, the hypermethylation status of candidate sites cg68167324 (OR = 3.168, 1.038–9.666) and cg24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; conversely, the hypermethylation of sites cg157130156 (OR = 0.361, 0.135–0.966) and cg89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. Conclusions The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester is associated with GDM pathogenesis, and has potential as a predictor of GDM.


2020 ◽  
Vol 8 (1) ◽  
pp. e000802 ◽  
Author(s):  
Chuyao Jin ◽  
Lizi Lin ◽  
Na Han ◽  
Zhiling Zhao ◽  
Zheng Liu ◽  
...  

ObjectiveTo examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.Research design and methodsA total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case–control study. Fasting venous blood samples were collected at the prenatal visit of the first trimester and during OGTT of the second trimester. Plasma concentration of fetuin-A and insulin was determined.ResultsThe plasma fetuin-A concentration in women with GDM was significantly higher than NGT controls in both the first trimester (medians: 403.0 pg/mL vs 273.4 pg/mL; p<0.05) and the second trimester (medians: 475.7 pg/mL vs 290.8 pg/mL; p<0.05) and notably increased from the first to the second trimester. Multivariate linear regression analysis showed that the change in fetuin-A concentration was associated with the changes in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, and HOMA of β-cell function (HOMA-β) (p<0.05). The highest quartile of the increase in fetuin-A concentration from the first to the second trimester was associated with a higher risk of developing GDM compared with the lowest quartile (OR 2.14; 95% CI 1.05 to 4.37).ConclusionsThe dynamic change in fetuin-A levels was associated with the changes in insulin resistance and β-cell function from the first to the second trimester, and was associated with an increased risk of the development of GDM, indicating that fetuin-A could be a biomarker to predict the risk of GDM.Trial registration numberNCT03814395.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Shujuan Ma ◽  
Chuhao Guo ◽  
Jiayue Zhang ◽  
Sisi Long ◽  
Hongzhuan Tan ◽  
...  

ELABELA (ELA) is considered to be implicated in the pathophysiology of preeclampsia (PE), since ELA-deficient mice exhibited PE-like symptoms and infusion of exogenous ELA normalized the gestational hypertension (GH) and proteinuria. However, no evidence show that circulating ELA is deficient in early placental development among women who destined to develop GH/PE. This nested case-control study was conducted to investigate the association between serum ELA concentration in early pregnancy and the risk of later GH/PE. Participants were recruited and sampled in 10-14+6 weeks of gestation. Definite GH/PE cases were matched 1 : 3 to controls with respect to age and gestational age. Serum concentration of ELA was measured using enzyme immunoassay. Women with later GH ( N = 28 ) had a slightly lower median concentration of ELA (46.72 ng/mL versus 53.54 ng/mL), while those with later PE ( N = 16 ) had a slightly higher median concentration of ELA (74.8 ng/mL versus 66.30 ng/mL) compared to the controls. Yet, both the increments did not reach statistically significant difference (GH: P = 0.380 , PE: P = 0.799 ). ELA serum concentrations were unchanged in first trimester in women with GH/PE. Further studies are still needed to identify the dynamic changes in serum ELA concentrations during the whole pregnancy, especially in those with pregnancy-induced hypertensive disorders.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Maria P. H. Koster ◽  
Rob J. Vreeken ◽  
Amy C. Harms ◽  
Adrie D. Dane ◽  
Sylwia Kuc ◽  
...  

Objective. To expand the search for preeclampsia (PE) metabolomics biomarkers through the analysis of acylcarnitines in first-trimester maternal serum.Methods. This was a nested case-control study using serum from pregnant women, drawn between 8 and 14 weeks of gestational age. Metabolites were measured using an UPLC-MS/MS based method. Concentrations were compared between controls (n=500) and early-onset- (EO-) PE (n=68) or late-onset- (LO-) PE (n=99) women. Metabolites with a false discovery rate <10% for both EO-PE and LO-PE were selected and added to prediction models based on maternal characteristics (MC), mean arterial pressure (MAP), and previously established biomarkers (PAPPA, PLGF, and taurine).Results. Twelve metabolites were significantly different between EO-PE women and controls, with effect levels between −18% and 29%. For LO-PE, 11 metabolites were significantly different with effect sizes between −8% and 24%. Nine metabolites were significantly different for both comparisons. The best prediction model for EO-PE consisted of MC, MAP, PAPPA, PLGF, taurine, and stearoylcarnitine (AUC = 0.784). The best prediction model for LO-PE consisted of MC, MAP, PAPPA, PLGF, and stearoylcarnitine (AUC = 0.700).Conclusion. This study identified stearoylcarnitine as a novel metabolomics biomarker for EO-PE and LO-PE. Nevertheless, metabolomics-based assays for predicting PE are not yet suitable for clinical implementation.


2018 ◽  
Vol 103 (7) ◽  
pp. 2447-2456 ◽  
Author(s):  
Shristi Rawal ◽  
Michael Y Tsai ◽  
Stefanie N Hinkle ◽  
Yeyi Zhu ◽  
Wei Bao ◽  
...  

Abstract Context T3 is the biologically active thyroid hormone involved in glucose metabolism. The free T3 (fT3)/free T4 (fT4) ratio, a marker indicating conversion of fT4 to fT3, is also implicated in glucose homeostasis. Objective To examine associations of fT3 and the fT3/fT4 ratio with gestational diabetes mellitus (GDM). Design In a case-control study, thyroid markers (fT3, fT4, TSH) were measured and the fT3/fT4 ratio was derived across four visits in pregnancy, including first (gestational weeks 10 to 14) and second (weeks 15 to 26) trimester. Conditional logistic regression adjusting for thyroid autoimmunity status and major GDM risk factors estimated trimester-specific associations of thyroid markers with subsequent GDM risk. Setting Twelve US clinical centers. Participants One hundred seven GDM cases and 214 non-GDM controls from a multiracial pregnancy cohort of 2802 women. Main Outcome Measures GDM diagnosis ascertained from medical records. Results Both fT3 and the fT3/fT4 ratio were positively associated with GDM: adjusted OR (95% CI) comparing the highest vs lowest fT3 quartile was 4.25 (1.67, 10.80) at the first trimester and 3.89 (1.50, 10.10) at the second trimester. Similarly, the corresponding risk estimates for the fT3/fT4 ratio were 8.63 (2.87, 26.00) and 13.60 (3.97, 46.30) at the first and second trimester, respectively. Neither TSH nor fT4 was significantly associated with GDM. Conclusions Higher fT3 levels, potentially resulting from de novo synthesis or increased fT4 to fT3 conversion, may be an indicator of GDM risk starting early in pregnancy.


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