New biomarkers for the detection of fetal death derived from large-scale proteomic analysis of maternal plasma
subject: angiogenesis; aptamer; biomarker; blood proteins; DNAJB9 protein; fetal death; glucose-6-phosphate 1-dehydrogenase; glycoprotein hormones alpha chain; hepcidin; high-throughput screening assay; placental growth factor; proteome; RNA polymerase III subunit C10; soluble fms-like tyrosine kinase 1; transcobalamin 2; vascular endothelial growth factor receptor-1
description: Background Normal pregnancy involves the modulation of thousands of maternal plasma proteins, and protein values not within the normal range may indicate the development of adverse pregnancy outcomes. A decrease in placental growth factor and an increase in soluble fms-like tyrosine kinase 1 in maternal plasma were shown to be associated with fetal death at the time of diagnosis and to predict this devastating pregnancy outcome at 24 to 28 weeks of gestation. However, these proteomic dysregulations are also present in other obstetrical syndromes, and more specific and sensitive biomarkers are needed to implement preventive strategies. Objective This study aimed to identify candidate protein biomarkers that can improve the prediction of fetal death relative to placental growth factor and soluble fms-like tyrosine kinase 1. Study Design This retrospective case-control study included 38 patients who experienced fetal death (cases) and 23 patients with uncomplicated pregnancies (controls). Plasma samples were collected at the time of diagnosis (2041 weeks of gestation) from cases and during routine care from gestational agematched controls. An aptamer-based multiplex assay was used to measure the abundance of >7000 protein analytes. Differential protein abundance was assessed using linear models with adjustment for gestational age at sample collection. Significance was inferred using a moderated t test adjusted P value of <.1 and a fold change of >1.25. Hypergeometric tests were performed to identify gene ontology biological processes enriched among proteins with significant changes in abundance. Random forest models were trained and evaluated via cross-validation to distinguish between fetal death cases and controls and to pinpoint the most salient predictors. Results Among the 7146 protein assays tested, 97 assays (1.4%) corresponding to 87 unique proteins differed significantly in abundance between fetal death cases and controls: 63 of 87 proteins (72%) were less abu…
creator: Romero, Roberto; Bhatti, Gaurav; Chaiworapongsa, Tinnakorn; Gomez-Lopez, Nardhy; Meyyazhagan, Arun; Chaemsaithong, Piya; Jung, Eunjung; Awonuga, Awoniyi O.; Kim, Yeon Mee; Gudicha, Dereje W.; Kim, Chong Jai; Bryant, David R.; Hassan, Sonia S.; Tarca, Adi L.
source: American Journal of Obstetrics and Gynecology;
publisher: Elsevier Inc.
date: 01-01-2026
rights: Restricted Access; Hardcopy may be available in the library
relation: ISSN: 29378; CODEN: AJOGA
format: online
language: English
type: Article
coverage: Romero R., Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI, United States, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, United States, Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, United States, George Washington University School of Medicine and Health Sciences, Washington, DC, United States; Bhatti G., Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States; Chaiworapongsa T., Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI, United States, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States; Gomez-Lopez N., Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI, United States, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States, Departments of Obstetrics and Gynecology and Pathology and Immunology, Center for Reproductive Health Sciences, Washington University School of Medicine, St. Louis, MO, United States; Meyyazhagan A., Pregnancy Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI, United States, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States, Department of Life Sciences, Christ University, Bengaluru, India; …