Abstract:Objective To investigate the changes in expression levels of microRNA-138-5p (miR-138-5p), autotaxin (ATX), and heme oxygenase-1 (HO-1) before and after less invasive surfactant administration (LISA) combined with dual positive airway pressure (DuoPAP) therapy and their prognostic values in neonates with acute respiratory distress syndrome (ARDS).Methods A total of 80 neonates with ARDS admitted to our hospital from October 2022 to October 2024 were included, all of whom received LISA combined with DuoPAP therapy. According to prognosis, they were divided into a poor prognosis group (n = 19) and a good prognosis group (n = 61). General clinical data and the changes in miR-138-5p, ATX, and HO-1 levels before and after treatment were compared between the two groups. Logistic regression analysis was used to identify factors influencing prognosis in neonates with ARDS, and receiver operating characteristic (ROC) curves were constructed to assess the prognostic values of changes in miR-138-5p, ATX, and HO-1 levels before and after LISA combined with DuoPAP therapy.Results The gestational age, birth weight, and 5-min Apgar scores were lower in the poor prognosis group than in the good prognosis group, whereas the incidence of sepsis, white blood cell count, SNAPPE-II scores, and the proportion of NICU stay ≥ 14 days were higher in the poor prognosis group. The levels of miR-138-5p and HO-1 were lower in the poor prognosis group than in the good prognosis group, while ATX levels were higher in the poor prognosis group. In addition, the differences in miR-138-5p, ATX, and HO-1 levels before and after treatment were all smaller in the poor prognosis group compared with the good prognosis group. Multivariable logistic regression analysis showed that lower gestational age [O^R = 0.763 (95% CI: 0.598, 0.975) ], lower 5-min Apgar scores [O^R = 0.476 (95% CI: 0.283, 0.800) ], concomitant sepsis [O^R = 4.433 (95% CI: 1.591, 12.355) ], higher SNAPPE-II scores [O^R = 1.536 (95% CI: 1.014, 2.329) ], longer NICU stay [O^R = 5.989 (95% CI: 1.874, 19.145) ], smaller pre- and post-treatment difference in miR-138-5p levels [O^R = 0.344 (95% CI: 0.146, 0.806) ], smaller pre- and post-treatment difference in ATX levels [O^R = 0.977 (95% CI: 0.956, 0.999) ], and smaller pre- and post-treatment difference in HO-1 levels [O^R = 0.947 (95% CI: 0.898, 0.998) ] were all risk factors for poor prognosis in children with ARDS (P < 0.05). ROC curve analysis demonstrated that the combined detection of pre- and post-treatment differences in miR-138-5p, ATX, and HO-1 levels showed the highest predictive performance, with a sensitivity of 94.7% (95% CI: 0.740, 0.999) and a specificity of 98.4% (95% CI: 0.912, 1.000).Conclusion Changes in miR-138-5p, ATX, and HO-1 levels before and after LISA combined with DuoPAP therapy have significant prognostic values in neonates with ARDS.