539 - Comparative Effectiveness of Two Fraction of Inspired Oxygen Thresholds for Surfactant Administration in Very Preterm Infants with Respiratory Distress Syndrome: a target trial emulation cohort study

Publication Number: 3520.539

Run Yang, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, China (People's Republic); Jie yang, Fudan Children's Hospital, Shanghai, Shanghai, China (People's Republic); Liang Gao, Women and Children’s Hospital, School of Medicine, Xiamen university, Xiamen, Fujian, China (People's Republic); Shibin Tu, Jiangxi Maternal and Child Hospital, Nanchang, Jiangxi, China (People's Republic); Wenyan Tang, Jiangxi Maternal and Child Hospital, Nanchang, Jiangxi, China (People's Republic); Lin Yuan, Children's Hospital of Fudan University, Shanghai, Shanghai, China (People's Republic); Kaizhen Liu, Children's Hospital of Chongqing Medical University, Chongqing, Chongqing, China (People's Republic)

Background: The optimal fraction of inspired oxygen (FiO₂) threshold for pulmonary surfactant (PS) in infants with respiratory distress syndrome (RDS) remains inconsistent and crucial. This study assessed comparative outcomes of PS at different FiO2 thresholds (0.25–0.30 versus 0.31-0.40) on a large-scale nationwide real-world database.

Objective: To evaluate the association between initiating PS treatment at different FiO2 thresholds (0.25–0.30 versus 0.31-0.40) and non-invasive ventilation failure in very preterm infants with RDS based on a large-scale nationwide real-world database.

Design/Methods: A cohort study of 3,221 patients was analyzed from 102 tertiary neonatal intensive care units in China to emulate a double-arm randomized clinical trial. Eligible subjects were inborn infants born at 26⁺⁰–31⁺⁶ weeks' gestation from January 2022 to December 2023 meeting: (1) RDS diagnosis, (2) PS administration, (3) noninvasive ventilation (NIV) with FiO₂ 0.25–0.30 at admission, (4) treatment initiation ≤24 hours postnatal. Threshold assignment was evaluated after overlap weighting propensity scores to balance treatment adherence.

Results: Exposure to a FiO2 of 0.25-0.30 was associated with lower incidences of invasive mechanical ventilation (IMV) (OR, 0.54; 95%CI, 0.40-0.71) and redosing surfactant (OR, 0.61; 95%CI, 0.44-0.85). A significant reduction in the incidence requiring IMV within 72 hours and redosing of PS was observed in males and infants with an admission temperature of ≥36.5℃ exposed to a FiO2 threshold of 0.25-0.30. Major findings remained robust in four sensitivity analyses. The only exception was the scenario with a cut-off of 0.29 for the requirement for IMV.

Conclusion(s): Early PS administration at FiO₂ threshold of 0.25–0.30 may lower the risk of non-invasive ventilation failure. This provides real-world evidence on the comparative effectiveness of the FiO₂ threshold and may help strengthen implementation of guidelines into the management of RDS.