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Maternal plasma lipids are involved in the pathogenesis of preterm birth

BACKGROUND: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environm...

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Autores principales: Chen, Yile, He, Bing, Liu, Yu, Aung, Max T, Rosario-Pabón, Zaira, Vélez-Vega, Carmen M, Alshawabkeh, Akram, Cordero, José F, Meeker, John D, Garmire, Lana X
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847704/
https://www.ncbi.nlm.nih.gov/pubmed/35166340
http://dx.doi.org/10.1093/gigascience/giac004
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author Chen, Yile
He, Bing
Liu, Yu
Aung, Max T
Rosario-Pabón, Zaira
Vélez-Vega, Carmen M
Alshawabkeh, Akram
Cordero, José F
Meeker, John D
Garmire, Lana X
author_facet Chen, Yile
He, Bing
Liu, Yu
Aung, Max T
Rosario-Pabón, Zaira
Vélez-Vega, Carmen M
Alshawabkeh, Akram
Cordero, José F
Meeker, John D
Garmire, Lana X
author_sort Chen, Yile
collection PubMed
description BACKGROUND: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24–28 gestational weeks. RESULTS: A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e−04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth. CONCLUSIONS: Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.
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spelling pubmed-88477042022-02-17 Maternal plasma lipids are involved in the pathogenesis of preterm birth Chen, Yile He, Bing Liu, Yu Aung, Max T Rosario-Pabón, Zaira Vélez-Vega, Carmen M Alshawabkeh, Akram Cordero, José F Meeker, John D Garmire, Lana X Gigascience Research BACKGROUND: Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks, and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 women who experienced preterm birth and 69 controls who underwent full-term labor at 24–28 gestational weeks. RESULTS: A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows that the fatty acid and carene-enriched module has a significant positive association (P = 8e−04, FDR = 0.006) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among 7 machine-learning classifiers, the application of random forest achieved a highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Additional modeling using only the 19 spontaneous preterm births (sPTB) and controls identifies 16 sPTB markers, with an AUC of 0.89 in testing data. Half of the sPTB overlap with those markers for preterm births. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth. CONCLUSIONS: Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth. Oxford University Press 2022-02-15 /pmc/articles/PMC8847704/ /pubmed/35166340 http://dx.doi.org/10.1093/gigascience/giac004 Text en © The Author(s) 2022. Published by Oxford University Press GigaScience. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Chen, Yile
He, Bing
Liu, Yu
Aung, Max T
Rosario-Pabón, Zaira
Vélez-Vega, Carmen M
Alshawabkeh, Akram
Cordero, José F
Meeker, John D
Garmire, Lana X
Maternal plasma lipids are involved in the pathogenesis of preterm birth
title Maternal plasma lipids are involved in the pathogenesis of preterm birth
title_full Maternal plasma lipids are involved in the pathogenesis of preterm birth
title_fullStr Maternal plasma lipids are involved in the pathogenesis of preterm birth
title_full_unstemmed Maternal plasma lipids are involved in the pathogenesis of preterm birth
title_short Maternal plasma lipids are involved in the pathogenesis of preterm birth
title_sort maternal plasma lipids are involved in the pathogenesis of preterm birth
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847704/
https://www.ncbi.nlm.nih.gov/pubmed/35166340
http://dx.doi.org/10.1093/gigascience/giac004
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