Longitudinal Proteomic Analysis of Plasma across Healthy Pregnancies Reveals Indicators of Gestational Age.
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ABSTRACT:
SUBMITTER: Yohannes E
PROVIDER: S-EPMC9266720 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gestational diabetes mellitus (GDM) increases many health risks in offspring. The study aims to investigate the underlying mechanism in fetal risk of GDM.We collected maternal peripheral plasma and umbilical venous plasma samples from 4 GDM and 4 control patients during their delivery at a university-based women's hospital. An isobaric tag for relative and absolute quantitation-labeled proteomics analysis was performed. The enzyme-linked immunosorbent assay was used to confirm the change of cholesteryl ester transfer protein (CETP). Bioinformatic analysis was performed with Ingenuity Pathway Analysis (IPA) software package.We identified 19 up-regulated proteins and 15 down-regulated proteins in GDM peripheral plasma, 29 up-regulated proteins and 69 down-regulated proteins in GDM umbilical venous plasma. CETP concentration was significantly lower in both GDM peripheral plasma and umbilical venous plasma. Upstream regulator analysis predicted follicle-stimulating hormone (FSH) as the activated regulator of differentially expressed proteins.The protein profiles in both GDM peripheral plasma and umbilical venous plasma between normal and GDM patients were significantly different. The results indicated that CETP and FSH might associates with health problem of GDM offspring.
| S-EPMC6133416 | biostudies-literature
Project description:To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using the SOMAscan assay (SomaLogic, Boulder, CO, USA) in a population of 240 healthy men and women, 22-93 years old, who were disease- and treatment-free and had no physical and cognitive impairment. Using a p ? 3.83 × 10-5 significance threshold, 197 proteins were positively associated, and 20 proteins were negatively associated with age. Growth differentiation factor 15 (GDF15) had the strongest, positive association with age (GDF15; 0.018 ± 0.001, p = 7.49 × 10-56 ). In our sample, GDF15 was not associated with other cardiovascular risk factors such as cholesterol or inflammatory markers. The functional pathways enriched in the 217 age-associated proteins included blood coagulation, chemokine and inflammatory pathways, axon guidance, peptidase activity, and apoptosis. Using elastic net regression models, we created a proteomic signature of age based on relative concentrations of 76 proteins that highly correlated with chronological age (r = 0.94). The generalizability of our findings needs replication in an independent cohort.
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Project description:Small for gestational age (SGA) newborns are often born from hypertensive pregnancies. This study aimed to compare the systemic metabolism of cortisol (F) in pregnancies with SGA and appropriate for gestational age (AGA) infants, considering both the normotensive (NT) and hypertensive patients. We hypothesized that the disturbances in systemic metabolism of F in pre-eclampsia (PE) might be attributed not to hypertension only, but to SGA. The study included 117 pregnants in the third trimester, divided into groups: NT pregnancy and SGA neonate (SGA-NT); NT pregnancy and AGA neonate (AGA-NT; controls), and respective groups with PE: SGA-PE and AGA-PE. We assessed the glucocorticoid balance with the function of enzymes involved in systemic metabolism of F: 11?-hydroxysteroid dehydrogenase type 1 and 2 (11?-HSD1 and 11?-HSD2), 5?- and 5?-reductase. The enzymes' functions were estimated with the levels of F, cortisone (E), and their metabolites in plasma or urine, which we measured with HPLC-FLD and HPLC-MS/MS. The plasma F/E and urinary free F/E (UFF/UFE) ratios correlated significantly only in patients with the normal function of 5?- and 5?-reductase. The increased function of 11?-HSD2 was noted in all pre-eclamptic pregnancies. Increased function of 5?- and 5?-reductase was specific only for SGA-PE pregnancies, and the function of 5?-reductase was dependent on fetal sex. The SGA-NT pregnancies with male fetuses trended towards the higher function of renal 11?-HSD2 and 5?-reductase; SGA-NT pregnancies with female fetuses lacked any systemic glucocorticoid imbalance. In conclusion, systemic metabolism of F is the most intensive in pre-eclamptic pregnancies complicated by SGA with female fetuses. Our study supports the hypothesis about the different origins of PE and idiopathic intrauterine growth restriction and suggests the sex-specific mechanisms responsible for fetal growth restriction.
| S-EPMC6884581 | biostudies-literature
Project description:The significance of antibodies directed against paternal epitopes in the context of obstetric disorders is discussed controversially. In this study anti-HLA and anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n?=?101), preeclampsia (PE, n?=?55) and gestational diabetes (GDM, n?=?36) using antigen specific microbeads. While two thirds of the women with uneventful pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to 13 with a modest increase towards the end of pregnancy, women with PE showed an inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody binding strength was more pronounced in gestational week 14 to 17 in patients with PE compared to women with uneventful pregnancy (maximum median fluorescence intensity of the highest ranked positive bead 7403, IQR 2193-7938 vs. 1093, IQR 395-5689; p?=?0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67-0.93; p?=?0.002). Our data suggest a pathophysiological involvement of HLA antibodies in PE. HLA antibody quantification in early pregnancy may provide a useful tool to increase diagnostic awareness in women prone to develop PE.
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Project description:The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.
| S-EPMC8423760 | biostudies-literature
Project description:BACKGROUND:Gestational diabetes mellitus (GDM) is correlated with an increased risk of adverse perinatal outcomes for both the mother and offspring. Previous research has reported correlations between maternal dietary patterns and GDM, but such evidence for twin pregnancies is lacking. This study aimed to identify maternal dietary patterns in the second trimester and investigate their relationships with the risk of GDM among women who were pregnant with twins in China. METHODS:A longitudinal twin pregnancies birth cohort study of women who were pregnant with twins in China was conducted. Maternal dietary intake in the second trimester was recorded by using a food frequency questionnaire prior to the diagnosis of GDM among participants from the prospective twin pregnancies birth cohort in Chongqing City. GDM was diagnosed with a 75?g 2-h oral glucose tolerance test at 23-26?weeks of gestation. Dietary patterns were identified by principal components analysis, and the correlations between dietary pattern and GDM were examined using multivariable logistic regression analyses. RESULTS:Of the 324 participants, 101 (31.2%) were diagnosed with GDM. Four dietary patterns were identified: a vegetable-based pattern, a poultry-and-fruit-based pattern, a sweet-based pattern and a plant-protein-based pattern. Multivariate analysis showed that none of the dietary patterns were correlated with the risk of GDM among women who were pregnant with twins, but the sweet-based dietary pattern, which was associated with a higher GDM risk for quartile 4 versus quartile 1 (OR 2.69; 95% CI: 1.09, 6.66) among non-overweight women (prepregnancy BMI?<?24.0). CONCLUSION:Dietary patterns were not correlated with later GDM risk among women who were pregnant with twins in western China, whereas a high intake of sweets was associated with a higher risk for GDM among women who were not overweight prior to pregnancy. TRIAL REGISTRATION:ChiCTR-OOC-16008203. Retrospectively registered on 1 April 2016.
| S-EPMC7008526 | biostudies-literature
Project description:Background: If not detected and treated, gestational diabetes mellitus (GDM) can cause serious pregnancy complications such as macrosomia, preeclampsia, and fetal/neonatal mortality. Many studies have examined underlying contributing factors for GDM, including hypercoagulation. Factor XII (FXII) is a coagulation factor that increases throughout normal pregnancies, and we evaluated the relationship of GDM with FXII, FXIIa (activated FXII), and other coagulation parameter levels. GDM and macrosomia are closely related, but it is not known whether FXII could be an independent causal factor for macrosomia.Methods: In this prospective study, blood samples were taken from 69 pregnant women at the time of term delivery to determine levels of FXII, FXIIa, and other coagulation parameters. Based on the results, pregnancies fell into GDM, non-diabetic with macrosomia (M), or healthy (C [control]).Results: FXII concentration levels were significantly higher in GDM patients compared with the M and C groups. There were no significant differences when comparing FXIIa, activated partial thromboplastin time, prothrombin time (PT), and international normalized ratio. The GDM group saw a significant negative correlation between FXII concentrations and maternal pregestational body mass index (BMI) and BMI before delivery. In the M group, a positive correlation was observed between FXII concentrations and newborn weight and newborn weight percentile.Conclusions: An increase in FXII levels was observed in patients with gestational diabetes. Associations between coagulation parameters and GDM should be further analyzed to define the mechanisms of GDM and possible treatment modalities.Trial registration: Our study has been registered at clinicaltrials.gov ( NCT03583216 ). Registered on July 11, 2018.
| S-EPMC7709445 | biostudies-literature
Project description:Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 × 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
| S-EPMC4459393 | biostudies-literature
Project description:A current major obstacle is that no reliable screening markers exist to detect pregnancies at risk for preeclampsia. Quantitative proteomic analysis employing isobaric labelling (iTRAQ) has been suggested to be suitable for the detection of potential plasma biomarkers, a feature we recently verified in analysis of pregnancies with Down syndrome foetuses. We have now examined whether this approach could yield biomarkers to screen pregnancies at risk for preeclampsia. In our study, we used maternal plasma samples obtained at 12 weeks of gestation, six from women who subsequently developed preeclampsia and six with uncomplicated deliveries. In our analysis, we observed elevations in 10 proteins out of 64 proteins in the preeclampsia study group when compared to the healthy control group. These proteins included clusterin, fibrinogen, fibronectin, and angiotensinogen, increased levels of which are known to be associated with preeclampsia. An elevation in the immune-modulatory molecule, galectin 3 binding protein, was also noted. Our pilot study, therefore, indicates that quantitative proteomic iTRAQ analysis could be a useful tool for the detection of new preeclampsia screening markers.
| S-EPMC3335425 | biostudies-literature
Project description:BACKGROUND:Twin pregnancies are at increased risk for adverse outcomes and are associated with greater gestational weight gain compared to singleton pregnancies. Studies that disentangle the relationship between gestational duration, weight gain and adverse outcomes are needed to inform weight gain guidelines. We created charts of the mean, standard deviation and select percentiles of maternal weight gain-for-gestational age in twin pregnancies and compared them to singleton curves. METHODS:We abstracted serial prenatal weight measurements of women delivering uncomplicated twin pregnancies at Magee-Womens Hospital (Pittsburgh, PA, 1998-2013) and merged them with the hospital's perinatal database. Hierarchical linear regression was used to express pregnancy weight gain as a smoothed function of gestational age according to pre-pregnancy BMI category. Charts of week- and day-specific values for the mean, standard deviation, and percentiles of maternal weight gain were created. RESULTS:Prenatal weight measurements (median: 11 [interquartile range: 9, 13] per woman) were available for 1109 women (573 normal weight, 287 overweight, and 249 obese). The slope of weight gain was most pronounced in normal weight women and flattened with increasing pre-pregnancy BMI (e.g. 50th percentiles of 6.8, 5.7, and 3.6 kg at 20 weeks and 19.8, 18.1, and 14.4 at 37 weeks in normal weight, overweight, and obese women, respectively). Weight gain patterns in twins diverged from singletons after 17-19 weeks. CONCLUSIONS:Our charts provide a tool for the classification of maternal weight gain in twin pregnancies. Future work is needed to identify the range of weight gain associated with optimal pregnancy health outcomes.
| S-EPMC5902642 | biostudies-literature