Evolution of the umbilical cord blood proteome across gestational development

Leena B. Mithal; Nicola Lancki; Ted Ling-Hu; Young Ah Goo; Sebastian Otero; Nathaniel J. Rhodes; Byoung Kyu Cho; William A Grobman; Judd F. Hultquist; Denise Scholtens; Karen K L Mestan; Patrick C. Seed

doi:10.1038/s41598-024-84446-5

Evolution of the umbilical cord blood proteome across gestational development

Leena B. Mithal, Nicola Lancki, Ted Ling-Hu, Young Ah Goo, Sebastian Otero, Nathaniel J. Rhodes, Byoung Kyu Cho, William A Grobman, Judd F. Hultquist, Denise Scholtens, Karen K L Mestan, Patrick C. Seed

Research output: Contribution to journal › Article › peer-review

Abstract

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 25 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. These data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions.

Original language	English (US)
Article number	2233
Journal	Scientific reports
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41598-024-84446-5
State	Published - Dec 2025

Funding

This work was supported by funding from the NIH (NIAID K23AI139337 to LBM and NHLBI K23HL093302 to KGM), Gerber Foundation, Friends of Prentice, and Thrasher Research Fund. Additional support was provided by Northwestern University Clinical and Translational Sciences Institute (UL1TR001422), Perinatal Origins of Disease Research Program at Lurie Children\u2019s, and the NUCord Biorepository. Salary support for JFH and TL-H was provided by NIH/NIAID grants (R21AI163912, R01AI165236, R01AI150455, R01AI150998, and U19AI135964) and additional institutional support for the Center for Pathogen Genomics and Microbial Evolution. The funding sources had no role in the study design, data collection, analysis, interpretation, or writing of the report. The authors would like to acknowledge Erin Cullather, BS; Paul Martin Thomas, PhD; Aaron Hamvas, MD; and Thomas Shanley, MD for their support toward this work. Proteomics services were performed by the Northwestern Proteomics Core Facility, generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center, instrumentation award (S10OD025194) from NIH Office of Director, and the National Resource for Translational and Developmental Proteomics supported by P41 GM108569.

Keywords

Biomarker development
Cord blood
Immune development
Neonatal immunology
Prematurity
Proteomics

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41598-024-84446-5

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Evolution of the umbilical cord blood proteome across gestational development

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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