Neurodevelopmental outcomes of preterm infants after randomisation to initial resuscitation with lower (FiO2 ≤0.3) or higher (FiO2 ≥0.6) initial oxygen levels. An individual patient meta-analysis

In an individual patient meta-analysis of infants less than 32 weeks gestation, resuscitation with lower (<0.3) or higher (>0.6) initial FiO2 was not associated with risk of death or disability at 2 years. Objective To determine the effects of lower (<= 0.3) versus higher (>= 0.6) initial fractional inspired oxygen (FiO(2)) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants Design Meta-analysis of individual patient data from three randomised controlled trials. Setting Neonatal intensive care units. Patients 543 children Intervention Randomisation at birth to resuscitation with lower (<= 0.3) or higher (>= 0.6) initial FiO(2). Outcome measures Primary: death and/or NDI at 2 years of age. Secondary: post-hoc non-randomised observational analysis of death/NDI according to 5-minute oxygen saturation (SpO(2)) below or at/above 80%. Results By 2 years of age, 46 of 543 (10%) children had died. Of the 497 survivors, 84 (17%) were lost to follow-up. Bayley Scale of Infant Development (third edition) assessments were conducted on 377 children. Initial FiO(2) was not associated with difference in death and/or disability (difference (95% CI) -0.2%, -7% to 7%, p=0.96) or with cognitive scores <85 (2%, -5% to 9%, p=0.5). Five-minute SpO(2) >80% was associated with decreased disability/death (14%, 7% to 21%) and cognitive scores >85 (10%, 3% to 18%, p=0.01). Multinomial regression analysis noted decreased death with 5-minute SpO(2) >= 80% (odds (95% CI) 09.62, 0.98 to 0.96) and gestation (0.52, 0.41 to 0.65), relative to children without death or NDI. Conclusion Initial FiO(2) was not associated with difference in risk of disability/death at 2 years in infants <32 weeks' gestation but CIs were wide. Substantial benefit or harm cannot be excluded. Larger randomised studies accounting for patient differences, for example, gestation and gender are urgently needed.

Automated summary

In this study, resuscitation with lower or higher initial FiO2 was not associated with the risk of death or disability at 2 years in infants under 32 weeks gestation. However, the wide confidence intervals indicate that conclusive evidence is lacking, and larger randomized studies are urgently needed to further investigate the potential benefits or harms of different initial FiO2 levels on infant outcomes.