Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study

Abstract Understanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases...

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Autores principales:	E. W. Harville, Y.-Y. Li, K. Pan, S. McRitchie, W. Pathmasiri, S. Sumner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2860a4011ef4166ad2a9bdd63449dac
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spelling	oai:doaj.org-article:a2860a4011ef4166ad2a9bdd63449dac2021-12-02T13:30:17ZUntargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study10.1038/s41598-021-82804-12045-2322https://doaj.org/article/a2860a4011ef4166ad2a9bdd63449dac2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82804-1https://doaj.org/toc/2045-2322Abstract Understanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases of PTB; and 109 controls were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository. Metabotyping was conducted using liquid chromatography high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. Multivariable logistic regression was used to identify signals that differed between groups after controlling for confounders. Signals important to predicting HDP and PTB were matched to an in-house physical standards library and public databases. Pathway analysis was conducted using GeneGo MetaCore. Over 400 signals for endogenous and exogenous metabolites that differentiated cases and controls were identified or annotated, and models that included these signals produced substantial improvements in predictive power beyond models that only included known risk factors. Perturbations of the aminoacyl-tRNA biosynthesis, l-threonine, and renal secretion of organic electrolytes pathways were associated with both HDP and PTB, while pathways related to cholesterol transport and metabolism were associated with HDP. This untargeted metabolomics analysis identified signals and common pathways associated with pregnancy complications.E. W. HarvilleY.-Y. LiK. PanS. McRitchieW. PathmasiriS. SumnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q E. W. Harville Y.-Y. Li K. Pan S. McRitchie W. Pathmasiri S. Sumner Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
description	Abstract Understanding of causal biology and predictive biomarkers are lacking for hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). First-trimester serum specimens from 51 cases of HDP, including 18 cases of pre-eclampsia (PE) and 33 cases of gestational hypertension (GH); 53 cases of PTB; and 109 controls were obtained from the Global Alliance to Prevent Prematurity and Stillbirth repository. Metabotyping was conducted using liquid chromatography high resolution mass spectroscopy and nuclear magnetic resonance spectroscopy. Multivariable logistic regression was used to identify signals that differed between groups after controlling for confounders. Signals important to predicting HDP and PTB were matched to an in-house physical standards library and public databases. Pathway analysis was conducted using GeneGo MetaCore. Over 400 signals for endogenous and exogenous metabolites that differentiated cases and controls were identified or annotated, and models that included these signals produced substantial improvements in predictive power beyond models that only included known risk factors. Perturbations of the aminoacyl-tRNA biosynthesis, l-threonine, and renal secretion of organic electrolytes pathways were associated with both HDP and PTB, while pathways related to cholesterol transport and metabolism were associated with HDP. This untargeted metabolomics analysis identified signals and common pathways associated with pregnancy complications.
format	article
author	E. W. Harville Y.-Y. Li K. Pan S. McRitchie W. Pathmasiri S. Sumner
author_facet	E. W. Harville Y.-Y. Li K. Pan S. McRitchie W. Pathmasiri S. Sumner
author_sort	E. W. Harville
title	Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
title_short	Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
title_full	Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
title_fullStr	Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
title_full_unstemmed	Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
title_sort	untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a2860a4011ef4166ad2a9bdd63449dac
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Untargeted analysis of first trimester serum to reveal biomarkers of pregnancy complications: a case–control discovery phase study

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