A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas.

Autor: Rosenblatt KP; NX Prenatal Inc, Louisville, KY., Zhang Z; Departments of Pathology and Oncology, Center for Biomarker Discovery and Translation, Johns Hopkins University School of Medicine, Baltimore, MD., Doss R; NX Prenatal Inc, Louisville, KY., Gurnani PP; NX Prenatal Inc, Louisville, KY., Grobman WA; Department of Obstetrics and Gynecology, The Ohio State University School of Medicine, Columbus, OH., Silver RM; Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT., Parry S; Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA., Reddy UM; Department of Obstetrics and Gynecology, Columbia University School of Medicine, New York, NY., Cao S; Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN., Haas DM; Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN. Electronic address: dahaas@iu.edu.
Jazyk: angličtina
Zdroj: American journal of obstetrics and gynecology [Am J Obstet Gynecol] 2024 May 23. Date of Electronic Publication: 2024 May 23.
DOI: 10.1016/j.ajog.2024.05.032
Abstrakt: Background: Despite much research, advances in early prediction of spontaneous preterm birth (sPTB) has been slow. The evolving field of circulating microparticle (CMP) biology may identify novel blood-based, and clinically useful, biomarkers.
Objective: To test the ability of a previously identified, 7-marker set of CMP-derived proteins from the first trimester of pregnancy, in the form of an in vitro diagnostic multivariate index assay (IVDMIA), to stratify pregnant patients according to their risk for sPTB.
Study Design: We employed a previously validated set of CMP protein biomarkers, utilizing mass spectrometry assays and a nested case-control design in a subset of participants from the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b). We evaluated these biomarkers in the form of an IVDMIA to predict risk for sPTB at different gestational ages. Plasma samples collected at 9- to 13-weeks' gestation were analyzed. The IVDMIA assigned subjects to 1 of 3 sPTB risk categories: low risk (LR), moderate risk (MR), or high risk (HR). Independent validation on a set-aside set confirmed the IVDMIA's performance in risk stratification.
Results: Samples from 400 participants from the nuMoM2b cohort were used for the study; of these, 160 delivered<37 weeks and 240 delivered at term. Through Monte Carlo simulation in which the validation results were adjusted based on actual weekly sPTB incidence rates in the nuMoM2b cohort, the IVDMIA stratifications demonstrated statistically significant differences among the risk groups in time-to-event (birth) analysis (P<.0001). The incidence-rate adjusted cumulative risks of sPTB at ≤32 weeks' gestation were 0.4%, 1.6%, and 7.5%, respectively for the LR, MR, and HR groups, respectively. Compared to the LR group, the corresponding risk ratios of the IVDMIA assigned MR and HR group were 4.25 (95% confidence interval [CI] 2.2-7.9) and 19.92 (95% CI 10.4-37.4), respectively.
Conclusion: A first trimester CMP protein biomarker panel can be used to stratify risk for sPTB at different gestational ages. Such a multitiered stratification tool could be used to assess risk early in pregnancy to enable timely clinical management and interventions, and, ultimately, to enable the development of tailored care pathways for sPTB prevention.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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