Prognostic Utility of Pro-Oxidant-Antioxidant Balance in Preterm Neonates with Respiratory Distress Syndrome: Insights into Disease Severity and Developmental Outcomes

Background Oxidative stress plays an important role in the pathophysiology of respiratory distress syndrome (RDS) in preterm neonates. The pro-oxidant–antioxidant balance (PAB) assay provides an integrated measure of oxidative status; however, its association with RDS severity and long-term outcomes remains incompletely defined. This study aimed to evaluate PAB in preterm infants with and without RDS and to investigate its association with disease severity, bronchopulmonary dysplasia (BPD), and neurodevelopmental outcomes during a 2-year follow-up. Methods In this prospective cohort study, 300 preterm neonates (26–34 weeks’ gestation), including 137 with RDS and 163 controls, were enrolled at the neonatal intensive care unit of Ghaem Hospital, Mashhad, Iran. PAB levels were measured in umbilical cord blood collected at birth using the tetramethylbenzidine (TMB)-based assay described by Alamdari et al. Clinical severity, short-term outcomes including BPD, and neurodevelopmental outcomes at 24 months of corrected age assessed using the Denver Developmental Screening Test II (Denver II) were evaluated. Univariate logistic regression analysis was performed to assess the association between PAB levels and clinical outcomes. Respiratory distress syndrome (RDS) was diagnosed according to the criteria described in Fanaroff and Martin’s Neonatal-Perinatal Medicine. Bronchopulmonary dysplasia (BPD) was defined as oxygen dependency at 36 weeks’ postmenstrual age according to the National Institute of Child Health and Human Development (NICHD) criteria. Results Neonates with RDS had significantly higher PAB levels than controls ( p < 0.001). Higher PAB levels were significantly associated with greater disease severity. Elevated PAB levels were also significantly associated with abnormal neurodevelopmental outcomes at 24 months ( p = 0.013). PAB levels increased progressively across disease severity categories, ranging from 11.58 in controls to 93.77 in neonates with RDS complicated by BPD. Conclusion Elevated PAB levels at birth were significantly associated with greater RDS severity and adverse neurodevelopmental outcomes in preterm neonates. PAB may represent a promising adjunctive biomarker for early risk stratification; however, its clinical utility requires validation in larger multicenter prospective studies before routine clinical implementation can be recommended. These findings should be interpreted cautiously because only univariate analyses were performed.