Plasma Asymmetric Dimethylarginine as a Biomarker of Disease Severity and Therapeutic Response in Neonatal Persistent Pulmonary Hypertension: An Observational Prospective Case-Control Study.

Abstract

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening condition characterized by elevated pulmonary vascular resistance and impaired oxygenation. Endothelial dysfunction plays a central role in its pathophysiology. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been implicated in pulmonary vascular disease; however, its clinical utility as a biomarker of disease severity and therapeutic response in neonatal PPHN remains insufficiently defined. Methods: This prospective observational case-control study included neonates diagnosed with PPHN and age- and sex-matched healthy controls. Plasma ADMA levels were measured using enzyme-linked immunosorbent assay (ELISA). Clinical severity was assessed using oxygenation index (OI) and echocardiographic parameters. Associations between ADMA levels, disease severity, and therapeutic response were analyzed using correlation analysis, multivariable regression models, and receiver operating characteristic (ROC) curve analysis. Results: Neonates with PPHN demonstrated significantly elevated plasma ADMA levels compared with controls (p < 0.001). ADMA levels showed a positive correlation with oxygenation index and echocardiographic markers of pulmonary hypertension severity. Higher baseline ADMA concentrations were independently associated with increased disease severity after adjustment for relevant confounders. ROC curve analysis demonstrated good discriminatory performance of ADMA in identifying severe PPHN. Additionally, declining ADMA levels were associated with clinical improvement following standard therapeutic interventions. Conclusion: Plasma ADMA levels are significantly elevated in neonates with PPHN and correlate with disease severity and therapeutic response. ADMA may serve as a promising biomarker for risk stratification and monitoring in neonatal PPHN. Larger multicenter studies are warranted to validate these findings and explore its prognostic utility.