Plasma profiling of extremely preterm infants identifies the proteins and processes that shape BPD initiation in the first days of life

Background: The biological mediators which initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. This study aimed to (1)identify bronchopulmonary dysplasia (BPD) specific changes in plasma proteins in the first 72 hours of life and (2) assess the predicative capability of identified proteins in combination with known BPD risk factors. Methods: Mass spectrometry was performed on plasma samples obtained at 4-, 24- and 72-hours post-birth from 23 infants born before 29 weeks' gestation. Proteins whose abundance differed between infants with and without BPD were identified and bioinformatic analysis conducted to identify BPD-related biological categories and pathways. Binary logistic regression analysis tested BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added. Bootstrap resampling internally validated protein predictors and adjusted for overoptimism. Results: Key processes including coagulation, complement activation, development and extracellular matrix organisation were disturbed in the first days of life in the BPD group. 49 plasma proteins were identified which when combined with birth characteristics could predict BPD with an accuracy of 0.65-0.84 (optimism-adjusted C-index). Conclusions: Alterations in plasma proteins were detected from 4 hours of age in extremely preterm infants who later developed BPD. Protein biomarkers combined with three birth characteristics strongly predicted BPD development within the first 72 hours of life.