Incremental Predictive Value of Cord Blood Oxidative Stress Biomarkers for Neonatal Acute Respiratory Distress Syndrome After Meconium-Stained Amniotic Fluid Exposure

Abstract Neonatal acute respiratory distress syndrome (NARDS) develops in only a subset of neonates exposed to meconium-stained amniotic fluid (MSAF), and birth-time biological markers may improve early risk assessment. We evaluated whether umbilical cord blood oxidative stress biomarkers provide incremental predictive information beyond clinical variables in a single-center retrospective cohort. Of 182 neonates with intrapartum MSAF screened between January 2020 and January 2026, 168 were included and 50 developed NARDS within 7 days. Cord blood malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and superoxide dismutase (SOD) were measured by ELISA. A clinical logistic model was developed using LASSO-selected predictors, and the three biomarkers were added as a prespecified panel. Addition of MDA, 4-HNE, and SOD increased the AUC from 0.901 to 0.969 (difference 0.068, 95% CI 0.019–0.117; P = 0.006) and reduced the Brier score from 0.106 to 0.055. Optimism-corrected AUCs were 0.890 and 0.955 for the clinical and enhanced models, respectively, and the enhanced model showed greater net benefit across clinically relevant thresholds. Cord blood oxidative stress biomarkers provided incremental predictive information beyond birth-time clinical variables; external validation is required before individual risk estimation.