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 24 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. Furthermore, 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.

The authors have declared no competing interest.

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's, 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.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Boards of Northwestern University (STU00201858) and Lurie Children's Hospital (IRB 2018-2145) gave ethical approval for this work. All research activities were performed in accordance with the Declaration of Helsinki.

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The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD051974.