W181 - Mapping Neonatal Plasma Proteome Changes over the First 2 Days of Life at an Hourly Resolution

Abstract Text: Birth represents a dramatic shift from a quasi-sterile intrauterine life to an antigen-rich extrauterine environment. The transition from fetal immune tolerance to facing new immune challenges necessitates a significant immune system adaptation. Key components of the immune system circulate in plasma such that early adaptations are reflected by changes to the plasma proteome composition. We utilized a high-resolution liquid-chromatography and mass spectrometry (LC-MS) platform to define the proteomic changes that occur hourly during the first 48hours of human life. We collected >900 peripheral blood samples from 679 healthy term newborns in The Gambia, West Africa at day of life (DOL)0 and DOL1, calculated the precise time duration between blood collection and birth enabling mapping of the postnatal plasma proteome at hourly resolution. Using LC-MS-based plasma proteomics and multiplex cytokine assays, we characterized 324 proteins and cytokines unveiling distinct and dynamic changes in developmental proteome trajectories. Notable changes included fluctuations in the levels of heme proteins, fibrinogens, serpins, and orosomucoid. Many changes could not be accurately captured at the DOL resolution, suggesting the importance of the hour-of-life in studies focused on the first days of life. Additionally, we identified critical ontogenetic periods after birth in healthy newborns, independent of the 24-hour period, which provide support for an immune clock extending beyond pregnancy. Our study of the neonatal plasma proteome at hourly resolution provides insights into protein ordering, co-regulation, and critical periods immediately after birth highlighting the importance of time in future studies investigating immunity and antigen response in early life.