Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study

Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteom...

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Autores principales:	Julja Burchard, Ashoka D. Polpitiya, Angela C. Fox, Todd L. Randolph, Tracey C. Fleischer, Max T. Dufford, Thomas J. Garite, Gregory C. Critchfield, J. Jay Boniface, George R. Saade, Paul E. Kearney
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	preterm birth IBP4 SHBG biomarkers Medicine R
Acceso en línea:	https://doaj.org/article/0ce762e2134e431990fa9acca088a426
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spelling	oai:doaj.org-article:0ce762e2134e431990fa9acca088a4262021-11-11T17:42:26ZClinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study10.3390/jcm102150882077-0383https://doaj.org/article/0ce762e2134e431990fa9acca088a4262021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/5088https://doaj.org/toc/2077-0383Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteomic biomarker threshold of −1.37, corresponding to a ~two-fold increase or ~15% risk of sPTB, significantly stratified earlier deliveries. Guidelines for molecular tests advise replication in a second independent study. Here we tested whether the significant association between proteomic biomarker scores above the threshold and sPTB, and associated adverse outcomes, was replicated in a second independent study, the Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TREETOP). The threshold significantly stratified subjects in PAPR and TREETOP for sPTB (<i>p</i> = 0.041, <i>p</i> = 0.041, respectively). Application of the threshold in a Kaplan–Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (<i>p</i> < 001, <i>p</i> = 0.0016) and rate of hospital discharge for both neonate (<i>p</i> < 0.001, <i>p</i> = 0.005) and mother (<i>p</i> < 0.001, <i>p</i> < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (<i>p</i> = 0.0083,) and 7.4-fold higher (<i>p</i> = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.Julja BurchardAshoka D. PolpitiyaAngela C. FoxTodd L. RandolphTracey C. FleischerMax T. DuffordThomas J. GariteGregory C. CritchfieldJ. Jay BonifaceGeorge R. SaadePaul E. KearneyMDPI AGarticlepreterm birthIBP4SHBGbiomarkersMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5088, p 5088 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	preterm birth IBP4 SHBG biomarkers Medicine R
spellingShingle	preterm birth IBP4 SHBG biomarkers Medicine R Julja Burchard Ashoka D. Polpitiya Angela C. Fox Todd L. Randolph Tracey C. Fleischer Max T. Dufford Thomas J. Garite Gregory C. Critchfield J. Jay Boniface George R. Saade Paul E. Kearney Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
description	Preterm births are the leading cause of neonatal death in the United States. Previously, a spontaneous preterm birth (sPTB) predictor based on the ratio of two proteins, IBP4/SHBG, was validated as a predictor of sPTB in the Proteomic Assessment of Preterm Risk (PAPR) study. In particular, a proteomic biomarker threshold of −1.37, corresponding to a ~two-fold increase or ~15% risk of sPTB, significantly stratified earlier deliveries. Guidelines for molecular tests advise replication in a second independent study. Here we tested whether the significant association between proteomic biomarker scores above the threshold and sPTB, and associated adverse outcomes, was replicated in a second independent study, the Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TREETOP). The threshold significantly stratified subjects in PAPR and TREETOP for sPTB (<i>p</i> = 0.041, <i>p</i> = 0.041, respectively). Application of the threshold in a Kaplan–Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (<i>p</i> < 001, <i>p</i> = 0.0016) and rate of hospital discharge for both neonate (<i>p</i> < 0.001, <i>p</i> = 0.005) and mother (<i>p</i> < 0.001, <i>p</i> < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (<i>p</i> = 0.0083,) and 7.4-fold higher (<i>p</i> = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.
format	article
author	Julja Burchard Ashoka D. Polpitiya Angela C. Fox Todd L. Randolph Tracey C. Fleischer Max T. Dufford Thomas J. Garite Gregory C. Critchfield J. Jay Boniface George R. Saade Paul E. Kearney
author_facet	Julja Burchard Ashoka D. Polpitiya Angela C. Fox Todd L. Randolph Tracey C. Fleischer Max T. Dufford Thomas J. Garite Gregory C. Critchfield J. Jay Boniface George R. Saade Paul E. Kearney
author_sort	Julja Burchard
title	Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title_short	Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title_full	Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title_fullStr	Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title_full_unstemmed	Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title_sort	clinical validation of a proteomic biomarker threshold for increased risk of spontaneous preterm birth and associated clinical outcomes: a replication study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0ce762e2134e431990fa9acca088a426
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Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study

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