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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

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: Burchard, Julja, Polpitiya, Ashoka D., Fox, Angela C., Randolph, Todd L., Fleischer, Tracey C., Dufford, Max T., Garite, Thomas J., Critchfield, Gregory C., Boniface, J. Jay, Saade, George R., Kearney, Paul E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584743/
https://www.ncbi.nlm.nih.gov/pubmed/34768605
http://dx.doi.org/10.3390/jcm10215088
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author Burchard, Julja
Polpitiya, Ashoka D.
Fox, Angela C.
Randolph, Todd L.
Fleischer, Tracey C.
Dufford, Max T.
Garite, Thomas J.
Critchfield, Gregory C.
Boniface, J. Jay
Saade, George R.
Kearney, Paul E.
author_facet Burchard, Julja
Polpitiya, Ashoka D.
Fox, Angela C.
Randolph, Todd L.
Fleischer, Tracey C.
Dufford, Max T.
Garite, Thomas J.
Critchfield, Gregory C.
Boniface, J. Jay
Saade, George R.
Kearney, Paul E.
author_sort Burchard, Julja
collection PubMed
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 (p = 0.041, p = 0.041, respectively). Application of the threshold in a Kaplan–Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (p < 001, p = 0.0016) and rate of hospital discharge for both neonate (p < 0.001, p = 0.005) and mother (p < 0.001, p < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (p = 0.0083,) and 7.4-fold higher (p = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes.
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spelling pubmed-85847432021-11-12 Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study Burchard, Julja Polpitiya, Ashoka D. Fox, Angela C. Randolph, Todd L. Fleischer, Tracey C. Dufford, Max T. Garite, Thomas J. Critchfield, Gregory C. Boniface, J. Jay Saade, George R. Kearney, Paul E. J Clin Med Article 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 (p = 0.041, p = 0.041, respectively). Application of the threshold in a Kaplan–Meier analysis demonstrated significant stratification in each study, respectively, for gestational age at birth (p < 001, p = 0.0016) and rate of hospital discharge for both neonate (p < 0.001, p = 0.005) and mother (p < 0.001, p < 0.001). Above the threshold, severe neonatal morbidity/mortality and mortality alone were 2.2 (p = 0.0083,) and 7.4-fold higher (p = 0.018), respectively, in both studies combined. Thus, higher predictor scores were associated with multiple adverse pregnancy outcomes. MDPI 2021-10-29 /pmc/articles/PMC8584743/ /pubmed/34768605 http://dx.doi.org/10.3390/jcm10215088 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Burchard, Julja
Polpitiya, Ashoka D.
Fox, Angela C.
Randolph, Todd L.
Fleischer, Tracey C.
Dufford, Max T.
Garite, Thomas J.
Critchfield, Gregory C.
Boniface, J. Jay
Saade, George R.
Kearney, Paul E.
Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth and Associated Clinical Outcomes: A Replication Study
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584743/
https://www.ncbi.nlm.nih.gov/pubmed/34768605
http://dx.doi.org/10.3390/jcm10215088
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