A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas - 20/02/25
Abstract |
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.
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Key words : biomarker, circulating microparticles, nulliparas, prediction, spontaneous preterm birth
Plan
| K.P.R. and Z.Z. contributed equally to this work. |
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| K.P.R., R.D., and P.P.G. are employed by NX Prenatal. Z.Z. is a paid consultant to NX Prenatal Inc and contributed to this work in a personal capacity independent of his affiliation with Johns Hopkins University. W.A.G., R.M.S., S.R., U.M.R., S.C., and D.M.H. report no conflict of interest. |
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| This study was supported by grant funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD063036, RTI International; U10 HD063072, Case Western Reserve University; U10 HD063047, Columbia University; U10 HD063037, Indiana University; U10 HD063041, University of Pittsburgh; U10 HD063020, Northwestern University; U10 HD063046, University of California Irvine; U10 HD063048, University of Pennsylvania; and U10 HD063053, University of Utah. In addition, support was provided by respective Clinical and Translational Science Institutes to Indiana University (UL1TR001108) and University of California Irvine (UL1TR000153). This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. As a cooperative agreement funding mechanism, the NICDH Program Officer was involved in the design of the study but not in the performing of the study, collection of data, or this analysis. NIH employees who are authors on this manuscript were not involved in the primary writing but were involved in the final editing and do satisfy authorship requirements. Funding for all assays were provided by NX Prenatal. NX Prenatal paid for the assays and processing. Analyses were performed independently of NX Prenatal. |
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| Cite this article as: Rosenblatt KP, Zhang Z, Doss R, et al. A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas. Am J Obstet Gynecol 2025;232:319.e1-21. |
Vol 232 - N° 3
P. 319.e1-319.e21 - mars 2025 Retour au numéro
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