scholarly journals Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders?

2020 ◽  
Author(s):  
Nancy McBride ◽  
Sara L. White ◽  
Lucilla Poston ◽  
Diane Farrar ◽  
Jane West ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pregnant Women ◽  
Gestational Age ◽  
Prediction Models ◽  
External Validation ◽  
Area Under The Curve ◽  
Large For Gestational Age ◽  
List Type ◽  
Independent Validation ◽  
Pregnancy Smoking

AbstractBackgroundPrediction of pregnancy-related disorders is mostly done based on established and easily measured risk factors. However, these measures are at best moderate at discriminating between high and low risk women. Recent advances in metabolomics may provide earlier and more accurate prediction of women at risk of pregnancy-related disorders.Methods and FindingsWe used data collected from women in the Born in Bradford (BiB; n=8,212) and UK Pregnancies Better Eating and Activity Trial (UPBEAT; n=859) studies to create and validate prediction models for pregnancy-related disorders. These were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), large for gestational age (LGA) and preterm birth (PTB). We used ten-fold cross-validation and penalised regression to create prediction models. We compared the predictive performance of 1) risk factors (maternal age, pregnancy smoking status, body mass index, ethnicity and parity) to 2) nuclear magnetic resonance-derived metabolites (N = 156 quantified metabolites, collected at 24-28 weeks gestation) and 3) risk factors and metabolites combined. The multi-ethnic BiB cohort was used for training and testing the models, with independent validation conducted in UPBEAT, a study of obese pregnant women of multiple ethnicities.In BiB, discrimination for GDM, HDP, LGA and SGA was improved with the addition of metabolites to the risk factors only model. Risk factors area under the curve (AUC 95% confidence interval (CI)): GDM (0.69 (0.64, 0.73)), HDP (0.74 (0.70, 0.78)) and LGA (0.71 (0.66, 0.75)), and SGA (0.59 (0.56,0.63)). Combined AUC 95% (CI)): GDM (0.78 (0.74, 0.81)), HDP (0.76 (0.73, 0.79)) and LGA (0.75 (0.70, 0.79)), and SGA (0.66 (0.63,0.70)). For GDM, HDP, LGA, but not SGA, calibration was good for a combined risk factor and metabolite model. Prediction of PTB was poor for all models. Independent validation in UPBEAT at 24-28 weeks and 15-18 weeks gestation confirmed similar patterns of results, but AUC were attenuated. A key limitation was our inability to identify a large general pregnancy population for independent validation.ConclusionsOur results suggest metabolomics combined with established risk factors improves prediction GDM, HDP and LGA, when compared to risk factors alone. They also highlight the difficulty of predicting PTB, with all models performing poorly.Author SummaryBackgroundCurrent methods used to predict pregnancy-related disorders exhibit modest discrimination and calibration.Metabolomics may enable improved prediction of pregnancy-related disorders.Why Was This Study Done?We require tools to identify women with high-risk pregnancies earlier on, so that antenatal care can be more appropriately targeted at women who need it most and tailored to women’s needs and to facilitate early intervention.It has been suggested that metabolomic markers might improve prediction of future pregnancy-related disorders. Previous studies tend to be small and rarely undertake external validation.What Did the Researchers Do and Find?Using BiB (8,212 pregnant women of multiple ethnicities), we created prediction models, using established risk factors and 156 NMR-derived metabolites, for five pregnancy-related disorders. These were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), large for gestational age (LGA) and preterm birth (PTB). We sought external validation in UPBEAT (859 obese pregnant women).We compared the predictive discrimination (area under the curve - AUC) and calibration (calibration slopes) of the models. The prediction models we compared were 1) established risk factors (pregnancy smoking, maternal age, body mass index (BMI), maternal ethnicity and parity) 2) NMR-derived metabolites measured in the second trimester and 3) a combined model of risk factors and metabolites.Inclusion of metabolites with risk factors improved prediction of GDM, HDP, LGA and SGA in BiB. Prediction of PTB was poor with all models. Result patterns were similar in validation using UPBEAT, particularly for GDM and HDP, but AUC were attenuated.What Do These Findings Mean?These findings indicate that combining current risk factor and metabolomic data could improve the prediction of GDM, HDP, LGA and SGA. These findings need to be validated in larger, general populations of pregnant women.

scholarly journals Do nuclear magnetic resonance (NMR)-based metabolomics improve the prediction of pregnancy-related disorders? Findings from a UK birth cohort with independent validation

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Nancy McBride ◽  
Paul Yousefi ◽  
Sara L. White ◽  
Lucilla Poston ◽  
Diane Farrar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Fatty Acids ◽  
Nuclear Magnetic Resonance ◽  
Risk Factor ◽  
Magnetic Resonance ◽  
Gestational Age ◽  
Maternal Age ◽  
Prediction Models ◽  
Independent Validation ◽  
Pregnancy Smoking

Abstract Background Prediction of pregnancy-related disorders is usually done based on established and easily measured risk factors. Recent advances in metabolomics may provide earlier and more accurate prediction of women at risk of pregnancy-related disorders. Methods We used data collected from women in the Born in Bradford (BiB; n = 8212) and UK Pregnancies Better Eating and Activity Trial (UPBEAT; n = 859) studies to create and validate prediction models for pregnancy-related disorders. These were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), large for gestational age (LGA) and preterm birth (PTB). We used ten-fold cross-validation and penalised regression to create prediction models. We compared the predictive performance of (1) risk factors (maternal age, pregnancy smoking, body mass index (BMI), ethnicity and parity) to (2) nuclear magnetic resonance-derived metabolites (N = 156 quantified metabolites, collected at 24–28 weeks gestation) and (3) combined risk factors and metabolites. The multi-ethnic BiB cohort was used for training and testing the models, with independent validation conducted in UPBEAT, a multi-ethnic study of obese pregnant women. Results Maternal age, pregnancy smoking, BMI, ethnicity and parity were retained in the combined risk factor and metabolite models for all outcomes apart from PTB, which did not include maternal age. In addition, 147, 33, 96, 51 and 14 of the 156 metabolite traits were retained in the combined risk factor and metabolite model for GDM, HDP, SGA, LGA and PTB, respectively. These include cholesterol and triglycerides in very low-density lipoproteins (VLDL) in the models predicting GDM, HDP, SGA and LGA, and monounsaturated fatty acids (MUFA), ratios of MUFA to omega 3 fatty acids and total fatty acids, and a ratio of apolipoprotein B to apolipoprotein A-1 (APOA:APOB1) were retained predictors for GDM and LGA. In BiB, discrimination for GDM, HDP, LGA and SGA was improved in the combined risk factors and metabolites models. Risk factor area under the curve (AUC 95% confidence interval (CI)): GDM (0.69 (0.64, 0.73)), HDP (0.74 (0.70, 0.78)) and LGA (0.71 (0.66, 0.75)), and SGA (0.59 (0.56, 0.63)). Combined risk factor and metabolite models AUC 95% (CI): GDM (0.78 (0.74, 0.81)), HDP (0.76 (0.73, 0.79)) and LGA (0.75 (0.70, 0.79)), and SGA (0.66 (0.63, 0.70)). For GDM, HDP and LGA, but not SGA, calibration was good for a combined risk factor and metabolite model. Prediction of PTB was poor for all models. Independent validation in UPBEAT at 24–28 weeks and 15–18 weeks gestation confirmed similar patterns of results, but AUCs were attenuated. Conclusions Our results suggest a combined risk factor and metabolite model improves prediction of GDM, HDP and LGA, and SGA, when compared to risk factors alone. They also highlight the difficulty of predicting PTB, with all models performing poorly.

scholarly journals Do Mass Spectrometry-Derived Metabolomics Improve the Prediction of Pregnancy-Related Disorders? Findings from a UK Birth Cohort with Independent Validation

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 530
Author(s):  
Nancy McBride ◽  
Paul Yousefi ◽  
Ulla Sovio ◽  
Kurt Taylor ◽  
Yassaman Vafai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mass Spectrometry ◽  
Pregnancy Outcome ◽  
Prediction Models ◽  
Large For Gestational Age ◽  
Maternal Risk Factors ◽  
Good Discrimination ◽  
Maternal Risk ◽  
Independent Validation ◽  
Combined Models

Many women who experience gestational diabetes (GDM), gestational hypertension (GHT), pre-eclampsia (PE), have a spontaneous preterm birth (sPTB) or have an offspring born small/large for gestational age (SGA/LGA) do not meet the criteria for high-risk pregnancies based upon certain maternal risk factors. Tools that better predict these outcomes are needed to tailor antenatal care to risk. Recent studies have suggested that metabolomics may improve the prediction of these pregnancy-related disorders. These have largely been based on targeted platforms or focused on a single pregnancy outcome. The aim of this study was to assess the predictive ability of an untargeted platform of over 700 metabolites to predict the above pregnancy-related disorders in two cohorts. We used data collected from women in the Born in Bradford study (BiB; two sub-samples, n = 2000 and n = 1000) and the Pregnancy Outcome Prediction study (POPs; n = 827) to train, test and validate prediction models for GDM, PE, GHT, SGA, LGA and sPTB. We compared the predictive performance of three models: (1) risk factors (maternal age, pregnancy smoking, BMI, ethnicity and parity) (2) mass spectrometry (MS)-derived metabolites (n = 718 quantified metabolites, collected at 26–28 weeks’ gestation) and (3) combined risk factors and metabolites. We used BiB for the training and testing of the models and POPs for independent validation. In both cohorts, discrimination for GDM, PE, LGA and SGA improved with the addition of metabolites to the risk factor model. The models’ area under the curve (AUC) were similar for both cohorts, with good discrimination for GDM (AUC (95% CI) BiB 0.76 (0.71, 0.81) and POPs 0.76 (0.72, 0.81)) and LGA (BiB 0.86 (0.80, 0.91) and POPs 0.76 (0.60, 0.92)). Discrimination was improved for the combined models (compared to the risk factors models) for PE and SGA, with modest discrimination in both studies (PE-BiB 0.68 (0.58, 0.78) and POPs 0.66 (0.60, 0.71); SGA-BiB 0.68 (0.63, 0.74) and POPs 0.64 (0.59, 0.69)). Prediction for sPTB was poor in BiB and POPs for all models. In BiB, calibration for the combined models was good for GDM, LGA and SGA. Retained predictors include 4-hydroxyglutamate for GDM, LGA and PE and glycerol for GDM and PE. MS-derived metabolomics combined with maternal risk factors improves the prediction of GDM, PE, LGA and SGA, with good discrimination for GDM and LGA. Validation across two very different cohorts supports further investigation on whether the metabolites reflect novel causal paths to GDM and LGA.

scholarly journals Risk factors for large-for-gestational age infants in pregnant women with type 1 diabetes

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Astrid Morrens ◽  
Johan Verhaeghe ◽  
Christine Vanhole ◽  
Roland Devlieger ◽  
Chantal Mathieu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Pregnant Women ◽  
Gestational Age ◽  
Large For Gestational Age

Association between gestational glycemic profile and delivery with a large for gestational age baby in pregnant women with type 1 diabetes

2020 ◽  
Author(s):  
Ekaterine Inashvili ◽  
Natalia Asatiani ◽  
Ramaz Kurashvili ◽  
Elena Shelestova ◽  
Mzia Dundua ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Pregnant Women ◽  
Gestational Age ◽  
Large For Gestational Age ◽  
Glycemic Profile

scholarly journals Incidence, Risk Factors, and Outcomes of Preterm and Early Term Births: A Population-Based Register Study

2021 ◽  
Vol 18 (11) ◽  
pp. 5865
Author(s):  
Salma Younes ◽  
Muthanna Samara ◽  
Rana Al-Jurf ◽  
Gheyath Nasrallah ◽  
Sawsan Al-Obaidly ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hospital Mortality ◽  
Gestational Age ◽  
Neonatal Intensive Care ◽  
Population Based ◽  
Incidence Rates ◽  
Large For Gestational Age ◽  
Mortality And Morbidity ◽  
Early Term ◽  
Incidence Risk

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar <7 at 1 and 5 minutes and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.

scholarly journals Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Espen Jimenez-Solem ◽  
Tonny S. Petersen ◽  
Casper Hansen ◽  
Christian Hansen ◽  
Christina Lioma ◽  
...  
Keyword(s):  
Prediction Models ◽  
Severe Disease ◽  
External Validation ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Mortality Prediction ◽  
Icu Admission ◽  
Risk Of Death ◽  
Online Risk ◽  
The United Kingdom

AbstractPatients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics—Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.

Abstract 210: Effects of Indication for Veno-Arterial Extracorporeal Membrane Oxygenation on Predictive Value of Save Score

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Marinos Kosmopoulos ◽  
Jason A Bartos ◽  
Demetris Yannopoulos
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Roc Curve ◽  
Predictive Value ◽  
Prediction Models ◽  
External Validation ◽  
Area Under The Curve ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Membrane Oxygenation ◽  
Survival Estimation ◽  
Va Ecmo

Introduction: Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO) has emerged as a prominent tool for management of patients with Inability to Wean Off Cardiopulmonary Bypass (IWOCB), extracorporeal cardiopulmonary resuscitation (eCPR) or refractory cardiogenic shock (RCS). The high mortality that is still associated with these diseases urges for the development of reliable prediction models for mortality after cannulation. Survival After VA ECMO (SAVE) Score consists one of the most widely used prediction tools and the only model with external validation. However, its predictive value is still under debate. Hypothesis: Whether VA ECMO indication affects the predictive value of SAVE Score. Methods: 317 patients treated with VA ECMO in a quaternary center (n= 52 for IWOCB, n=179 for eCPR and n=86 for RCS) were retrospectively assessed for differences in SAVE Score and their primary outcomes. The Receiver Operating Characteristic (ROC) curve for SAVE Score and mortality was calculated separately for each VA ECMO indication. Results: The three groups had significant differences in SAVE Score (p<0.01) without significant differences in mortality (p=0.176). ROC Curve calculation indicated significant differences in predictive value of SAVE Score for survival among its different indications. (Area Under the Curve= 81.69% for IWOCB, 53.79% for eCPR and 69.46% for RCS). Conclusion: VA ECMO indication markedly affects the predictive value of SAVE Score. Prediction of primary outcome in IWOCB patients was reliable. On the contrary, routine application for survival estimation in eCPR patients is not supported from our results.

Abstract 196: Development and Validation of Machine Learning-based Race-specific Models to Predict 10-year Risk of Heart Failure: A Multi-cohort Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Matthew W Segar ◽  
Byron Jaeger ◽  
Kershaw V Patel ◽  
Vijay Nambi ◽  
Chiadi E Ndumele ◽  
...  
Keyword(s):  
Machine Learning ◽  
Risk Factors ◽  
Heart Failure ◽  
Risk Prediction ◽  
Prediction Models ◽  
External Validation ◽  
Superior Performance ◽  
Risk Models ◽  
Black And White ◽  
White Adults

Introduction: Heart failure (HF) risk and the underlying biological risk factors vary by race. Machine learning (ML) may improve race-specific HF risk prediction but this has not been fully evaluated. Methods: The study included participants from 4 cohorts (ARIC, DHS, JHS, and MESA) aged > 40 years, free of baseline HF, and with adjudicated HF event follow-up. Black adults from JHS and white adults from ARIC were used to derive race-specific ML models to predict 10-year HF risk. The ML models were externally validated in subgroups of black and white adults from ARIC (excluding JHS participants) and pooled MESA/DHS cohorts and compared to prior established HF risk scores developed in ARIC and MESA. Harrell’s C-index and Greenwood-Nam-D’Agostino chi-square were used to assess discrimination and calibration, respectively. Results: In the derivation cohorts, 288 of 4141 (7.0%) black and 391 of 8242 (4.7%) white adults developed HF over 10 years. The ML models had excellent discrimination in both black and white participants (C-indices = 0.88 and 0.89). In the external validation cohorts for black participants from ARIC (excluding JHS, N = 1072) and MESA/DHS pooled cohorts (N = 2821), 131 (12.2%) and 115 (4.1%) developed HF. The ML model had adequate calibration and demonstrated superior discrimination compared to established HF risk models (Fig A). A consistent pattern was also observed in the external validation cohorts of white participants from the MESA/DHS pooled cohorts (N=3236; 100 [3.1%] HF events) (Fig A). The most important predictors of HF in both races were NP levels. Cardiac biomarkers and glycemic parameters were most important among blacks while LV hypertrophy and prevalent CVD and traditional CV risk factors were the strongest predictors among whites (Fig B). Conclusions: Race-specific and ML-based HF risk models that integrate clinical, laboratory, and biomarker data demonstrated superior performance when compared to traditional risk prediction models.

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