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Project description:Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. Here we investigated cell-free DNA and RNA content of 102 maternal and 25 cord plasma samples. Employing a novel deconvolution methodology, we found that during the first trimester, placenta-specific DNA increased prior to the subsequent development of gestational diabetes with no change in patients with preeclampsia while decreasing with maternal obesity. Moreover, using cell-free RNA sequencing, APOs revealed seventy-one differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3 and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features.
2020-10-19 | GSE154348 | GEO
Project description:Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. Here we investigated cell-free DNA and RNA content of 102 maternal and 25 cord plasma samples. Employing a novel deconvolution methodology, we found that during the first trimester, placenta-specific DNA increased prior to the subsequent development of gestational diabetes with no change in patients with preeclampsia while decreasing with maternal obesity. Moreover, using cell-free RNA sequencing, APOs revealed 71 differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3, and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features.
| S-EPMC8143248 | biostudies-literature
Project description:Although analysis of maternal plasma cell-free content has been employed for screening of genetic abnormalities within a pregnancy, limited attention has been paid to its use for the detection of adverse pregnancy outcomes (APOs) based on placental function. We investigated the cell-free RNA content of 102 maternal, 25 cord plasma samples and 7 non pregnant women as control. using cell-free RNA sequencing, APOs revealed seventy-one differentially expressed genes early in pregnancy. We noticed the upregulation of S100A8, MS4A3 and MMP8 that have been already associated with APOs but also the upregulation of BCL2L15 and the downregulation of ALPL that have never been associated with APOs. We constructed a classifier with a positive predictive ability (AUC) of 0.91 for APOs, 0.86 for preeclampsia alone and 0.64 for GDM. We conclude that placenta-specific cell-free nucleic acids during early gestation provide the possibility of predicting APOs prior to the emergence of characteristic clinical features.
2020-10-19 | GSE154377 | GEO
Project description:Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes
| PRJNA646065 | ENA
Project description:Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes [WGBS]
| PRJNA645920 | ENA
Project description:Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes [RNA-seq]
| PRJNA646066 | ENA
Project description:OBJECTIVE:To evaluate the association between gestational weight gain in twin pregnancies and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth, preterm birth before 32 weeks of gestation, cesarean delivery, and infant death within each prepregnancy body mass index (BMI) category. METHODS:Data in this population-based study came from Pennsylvania-linked infant birth and death records (2003-2013). We studied 54,836 twins born alive before 39 weeks of gestation. Total pregnancy weight gain (kg) was converted to gestational age-standardized z scores. Multivariable modified Poisson regression models stratified by prepregnancy BMI were used to estimate associations between z scores and outcomes. A probabilistic bias analysis, informed by an internal validation study, evaluated the effect of BMI and weight gain misclassification. RESULTS:Gestational weight gain z score was negatively associated with SGA and positively associated with LGA and cesarean delivery in all BMI groups. The relation between weight gain and preterm birth was U-shaped in nonobese women. An increased risk of infant death was observed for very low weight gain among normal-weight women and for high weight gain among women without obesity. Most excess risks of these outcomes were observed at weight gains at 37 weeks of gestation that are equivalent to less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity. The bias analysis supported the validity of the conventional analysis. CONCLUSION:Very low or very high weight gains were associated with the adverse outcomes we studied. If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes.
| S-EPMC6814560 | biostudies-literature
Project description:Disease diagnosis using cell-free DNA (cfDNA) has been an active research field recently. Most existing approaches perform diagnosis based on the detection of sequence variants on cfDNA; thus, their applications are limited to diseases associated with high mutation rate such as cancer. Recent developments start to exploit the epigenetic information on cfDNA, which could have substantially wider applications. In this work, we provide thorough reviews and discussions on the statistical method developments and data analysis strategies for using cfDNA epigenetic profiles, in particular DNA methylation, to construct disease diagnostic models. We focus on two important aspects: marker selection and prediction model construction, under different scenarios. We perform simulations and real data analysis to compare different approaches, and provide recommendations for data analysis.
| S-EPMC6556903 | biostudies-other
Project description:BackgroundLittle is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC).MethodsMethylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts.ResultsUsing genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4-79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis.ConclusionThe promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.
| S-EPMC6522894 | biostudies-literature
Project description:We aimed to describe the characteristics of adolescent pregnancy, determine its effect on adverse maternal and perinatal outcomes and explore whether that association varies with gestational age with the goal of proposing specific recommendations for adolescent health in China. This study included 2,366,559 women aged 10-24 years who had singleton pregnancies between 2012 and 2019 at 438 hospitals. Adolescent pregnancy was defined as younger than 20 years of age. We used multivariable logistic regression to estimate the effects. Women aged 20-24 years served as the reference group in all analyses. The proportion of rural girls with adolescent pregnancies rebounded after 2015 even though common-law marriage in rural areas decreased. Higher risks of eclampsia (adjusted odds ratio (aOR) 1.87, 95% confidence interval (CI) 1.57 ~ 2.23), severe anaemia (aOR 1.18, 95% CI 1.09 ~ 1.28), maternal near miss (MNM; aOR 1.24, 95% CI 1.12 ~ 1.37), and small for gestational age (SGA; aOR 1.30, 95% CI 1.28 ~ 1.33) were observed when gestational age was > 37 weeks. Adolescent pregnancy was independently associated with increased risks of other perinatal outcomes. Further implementation of pregnancy prevention strategies and improved health care interventions are needed to reduce adolescent pregnancies and prevent adverse fertility outcomes among adolescent women in China at a time when adolescent fertility rate is rebounding.
| S-EPMC8206124 | biostudies-literature