Bi-hourly plasma proteomics during the first 48 h of life in an African cohort reveals distinct periods and sex-dependent immune development.

Birth marks a sudden transition from a sterile intrauterine environment to one rich in pathogens, requiring rapid immune adaptation. Using mass spectrometry and immunoassays, we profile 324 plasma proteins, cytokines, and chemokines in 906 peripheral blood samples from 679 healthy, term, vaginally born Gambian neonates and an independent smaller validation cohort from Papua New Guinea. This proteomic analysis provides insights into plasma protein dynamics during the first 48 h of life at a bi-hourly resolution. The temporal analysis reveals non-linear trajectories, layering of immune system development, and distinct periods, all of which are inadequately described at the conventional day of life resolution. Significant sex-dependent immune system development is noticeable during the first 16 h after birth, which is also supported by a neonatal immuno-molecular clock for the earliest postnatal period. This study provides molecular insights into normal plasma protein ontogenies and developmental processes during the first two days of life.