Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis

Importance: Resuscitation with lower fractional inspired oxygen (FiO₂) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO₂on reducing mortality, severe morbidities, and oxygen saturations (SpO₂) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO₂. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO₂at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO₂was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO₂(OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO₂had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO₂(≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO₂(low certainty). High initial FiO₂is possibly associated with reduced mortality compared to intermediate initial FiO₂(very low certainty) but more evidence is required.