Original Investigation 

Targeted Oxygen for Initial Resuscitation of Preterm Infants: The TORPIDO 30/60 Randomized Clinical Trial

Ju Lee Oei, Adrienne Kirby, Javeed Travadi, et al

JAMA Published Online: December 10, 2025

doi: 10.1001/jama.2025.23327

Key Points

Question  Does initiating resuscitation of extremely preterm newborns with a higher level of fraction of inspired oxygen (Fio₂; 0.6) reduce risk of death or brain injury compared with a lower Fio₂ (0.3)?

Findings  This randomized clinical trial of 1469 infants born at 23 to 28 weeks’ gestation in 6 countries found no association between initial Fio₂ and death or brain injury at 36 weeks’ corrected gestational age (46.9% vs 47.8%).

Meaning  There was no difference in risk of brain injury or death after initiating resuscitation with an Fio₂ of 0.6 vs 0.3.

Abstract

Importance  The most effective initial fraction of inspired oxygen (Fio₂) for resuscitating preterm newborns is unknown.

Objective  To compare outcomes of newborns born at 23 to 28 weeks’ gestation resuscitated with initial Fio₂ of 0.6 vs 0.3.

Design, Setting, and Participants  Randomized clinical trial conducted in 31 maternity hospitals in 6 countries. Consent by waiver was obtained in Australia, certain institutions in India, and Malaysia; prospective informed consent was obtained in certain institutions in India and all institutions in Singapore, Spain, and the US. Infants due at 23 to 28 weeks’ gestation were randomized shortly before birth. Those with congenital abnormalities affecting oxygenation, neurodevelopment, or survival were excluded. Randomization was conducted from September 2018 to September 2024, with follow-up expected to close in September 2026.

Intervention  Infants were randomized (1:1) to receive an initial Fio₂ of 0.6 or 0.3; Fio₂ was titrated to meet standard targets for oxygen saturation by pulse oximetry in the first 10 minutes or for clinical needs. Clinicians and those assessing outcomes were not blinded to group assignment.

Main Outcomes and Measures  The primary outcome was death and brain injury at 36 weeks’ corrected gestational age; secondary outcomes were the individual components of the primary outcome.

Results  A total of 1641 newborns were randomized. The primary analysis included 728 newborns randomized to receive an Fio₂ of 0.6 and 741 to an Fio₂ of 0.3 after excluding 172 newborns, mostly for birth after 28 weeks’ gestation and transfer to another hospital before birth (54% female). Rates of escalation to Fio₂ of 1.0 were similar between the groups (Fio₂ of 0.6: 41%; Fio₂ of 0.3: 38%). Primary outcome information was ascertained in 1423 newborns (96.9%). Death or brain injury at 36 weeks’ corrected gestational age occurred in 330 of 703 newborns (46.9%) assigned to the Fio₂ of 0.6 group vs 344 of 720 (47.8%) assigned to the Fio₂ of 0.3 group (relative risk, 0.98 [95% CI, 0.89-1.09]).

Conclusions and Relevance  Initiating resuscitation of preterm infants with Fio₂ of 0.6 vs 0.3 did not affect the risk of death or brain injury by 36 weeks’ corrected gestational age. These results lay a foundation for future trials evaluating the effectiveness and safety of using higher initial Fio₂ levels for preterm infant resuscitation.

Trial Registration  ANZCTR Identifier: ACTRN12618000879268