Multi-domain laboratory biochemical profiling of pulmonary surfactant replacement therapy in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid of preterm infants with neonatal respiratory distress syndrome: A retrospective cohort study

Background: Neonatal respiratory distress syndrome (NRDS) remains a major cause of early morbidity in preterm infants. Although exogenous pulmonary surfactant (PS) replacement therapy has improved short-term respiratory outcomes, the laboratory biochemical alterations accompanying PS treatment across different body fluid compartments have not been fully characterised. This study aimed to describe multi-domain biochemical changes associated with PS replacement therapy in preterm infants with NRDS. Methods: A total of 99 preterm infants with NRDS admitted to our hospital from January 1 to December 31, 2025, were included and divided into the PS treatment group (n=47) and the control group (n=52) according to treatment strategy. Fifty biochemical indicators involving nine core biochemical pathways were measured in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid before treatment, 72 h after treatment, and 7 d after treatment. These pathways included bronchial development, intracranial injury, oxidative stress, inflammatory response, coagulation-fibrinolysis, vascular endothelial function, energy metabolism, hepatic function, and pulmonary surfactant function. Results: Before treatment, no significant differences were found in any biochemical indicators between the two groups (P>0.05). At 72 h and 7 d after treatment, the levels of markers related to bronchial epithelial injury, intracranial injury, oxidative injury, inflammatory response, coagulation-fibrinolytic disorder, and vascular endothelial injury were lower in the PS treatment group than in the control group (P<0.05). In contrast, indicators related to endogenous antioxidant capacity, pulmonary surfactant function, mitochondrial energy metabolism, and hepatic synthetic function were higher in the PS treatment group than in the control group (P<0.05). No significant changes were observed in the cerebrospinal fluid/serum S100 b ratio or serum pyruvate level at any time point in either group (P>0.05). These negative findings suggest that PS treatment was not associated with laboratory evidence of blood-brain barrier disruption and that pyruvate-related glycolytic homeostasis remained broadly stable in both groups. Conclusion: In this retrospective cohort, PS replacement therapy was associated with coordinated improvements in several biochemical domains in preterm infants with NRDS, including pulmonary surfactant function, oxidative-inflammatory status, coagulation-fibrinolytic balance, vascular endothelial markers, energy metabolism, and hepatic synthetic function. These findings provide exploratory laboratory evidence for multi-domain biochemical changes after PS treatment.