170 - Oxidant Stress Adducts Correlate with Cumulative Supplemental Oxygen Exposure and Bronchopulmonary Dysplasia

Adductomics is an exposure science approach that captures endogenous electrophiles associated with byproducts of oxidative reactions. The endogenous products formed via these oxidative reactions are referred to as adducts. Adducts in the blood are bound to the nucleophilic cysteine loci of human serum albumin, which has a 3-week half-life, allowing for more robust capture, quantification, and characterization of oxidative stress, an important pathogenic process in bronchopulmonary dysplasia (BPD).

Objective:

To identify oxidant stress adducts associated with cumulative supplemental oxygen (CSO) exposure preceding BPD.

Design/Methods:

A total of 209 extremely preterm and 51 healthy term infants were included. Cord blood was collected at birth in 211 infants. Serial postnatal blood was collected in a separate group at 1 week, 1 month and 36 weeks postmenstrual age (PMA; Figure 1). 103 infants had BPD (defined by modified NIH criteria). Plasma samples were analyzed using a tandem mass spectrometer. Adduct concentrations were log-transformed and normalized. CSO was calculated as the sum of the average daily supplemental oxygen (FiO₂-0.21) over the time interval leading up to each blood collection. Linear modeling was conducted in R (Ver. 4.0.3) using Bioconductor packages edgeR and limma. Models were adjusted for relevant clinical and demographic covariates and corrected for dual adduct concentrations (adj. P< 0.05).

Results: Among BPD vs. non-BPD infants, gestational age was 26.1±1.6w vs. 27.7±1.2w; birth weight was 854±202g vs. 1110±201g, respectively (P< 0.001). In targeted analysis, 49 unknown adducts and 56 annotated known adducts were detected. In cord blood, known direct oxidation products were associated with prematurity, BPD, and placental dysfunction. T3 dimer was exclusive to prematurity (P< 0.001). Cys34→Oxoalanine was exclusive to BPD (P< 0.001). Dehydrated Cys34 sulfinic acid plus methylation was associated with placental dysfunction (P< 0.001; Fig.2). In peripheral blood, there were 24 unknown adducts that were increased with BPD at 1 month of life (P< 0.05). Cys34→Oxoalanine—the same adduct increased in cord blood of infants who developed BPD—had a negative trend with CSO at 1 month and a positive trend with CSO at 36 weeks PMA. (Fig.3)

Conclusion(s): Serial adductomics revealed specific adducts that vary with placental dysfunction and supplemental oxygen— important exposures in BPD pathogenesis. These findings suggest that differences in the antioxidant capacity of individual preterm infants may contribute to variable observed responses to supplemental oxygen exposure and risk for BPD.